NAMPT inhibitors

Abstract
Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed.
Description
FIELD OF THE INVENTION

This invention pertains to compounds which inhibit the activity of NAMPT, compositions containing the compounds, and methods of treating diseases during which NAMPT is expressed.


BACKGROUND OF THE INVENTION

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a critical role in many physiologically essential processes (Ziegkel, M. Eur. J. Biochem. 267, 1550-1564, 2000). NAD is necessary for several signaling pathways including among others poly ADP-ribosylation in DNA repair, mono-ADP-ribosylation in both the immune system and G-protein-coupled signaling, and NAD is also required by sirtuins for their deacetylase activity (Garten, A. et al Trends in Endocrinology and Metabolism, 20, 130-138, 2008).


NAMPT (also known as pre-B-cell-colony-enhancing factor (PBEF) and visfatin) is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two pathways that salvage NAD.




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Increasing evidence suggests that NAMPT inhibitors have potential as anticancer agents. Cancer cells have a higher basal turnover of NAD and also display higher energy requirements compared with normal cells. Additionally, increased NAMPT expression has been reported in colorectal cancer (Van Beijnum, J. R. et al Int. J. Cancer 101, 118-127, 2002) and NAMPT is involved in angiogenesis (Kim, S R et al. Biochem. Biophys. Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPT have been shown to cause depletion of intracellular NAD+ levels and ultimately induce tumor cell death (Hansen, C M et al. Anticancer Res. 20, 42111-4220, 2000) as well as inhibit tumor growth in xenograft models (Olese, U. H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).


NAMPT inhibitors also have potential as therapeutic agents in inflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70, 8-11, 2010). For example, NAMPT is the predominant enzyme in T and B lymphocytes. Selective inhibition of NAMPT leads to NAD+ depletion in lymphocytes blocking the expansion that accompanies autoimmune disease progression whereas cell types expressing the other NAD+ generating pathways might be spared. A small molecule NAMPT inhibitor (FK866) has been shown to selectively block proliferation and induce apoptosis of activated T cells and was efficacious in animal models of arthritis (collagen induced arthritis) (Busso, N. et al. Plos One 3, e2267, 2008). FK866 ameliorated the manifestations of experimental autoimmune encephalomyelitis (EAE), a model of T-cell mediated autoimmune disorders. (Bruzzone, S et al. Plos One 4, e7897, 2009). NaMPT activity increases NF-kB transcriptional activity in human vascular endothelial cell, resulting in MMP-2 and MMP-9 activation, suggesting a role for NAMPT inhibitors in the prevention of inflammatory mediated complications of obesity and type 2 diabetes (Adya, R. et. Al. Diabetes Care, 31, 758-760, 2008).


SUMMARY OF THE INVENTION

One embodiment, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IB)




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or a therapeutically acceptable salt thereof, wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


Z is CH, C—F, C—Cl, C—Br, C—I or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is hydrogen, F, Cl, Br, or I;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I;


R11 at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


m is 4, 5, or 6; and


n is 1 or 2;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


In another embodiment of Formula (IB), R1 is NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (IB), R1 is CH2NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (IB), R1 is hydrogen; and R2 is CH2NHC(O)NHR3. In another embodiment of Formula (IB), R1 is hydrogen; and R2 is CH2NHC(O)R3. In one embodiment of Formula (IB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In one embodiment of Formula (IB), R1 is NHC(O)NHR3; R2 is hydrogen; and R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In one embodiment of Formula (IB), R1 is CH2NHC(O)R3; R2 is hydrogen; and R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In one embodiment of Formula (IB), R1 is hydrogen; R2 is CH2NHC(O)NHR3; and R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In one embodiment of Formula (IB), R1 is hydrogen; R2 is CH2NHC(O)R3; and R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IB), R1 is NHC(O)NHR3; R2 is hydrogen; and R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IB), R1 is CH2NHC(O)R3; R2 is hydrogen; and R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IB), R1 is hydrogen; R2 is CH2NHC(O)NHR3; and R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IB), R1 is hydrogen; R2 is CH2NHC(O)R3; and R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


Still another embodiment pertains to compounds, which are

  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-7-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenylethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(morpholin-4-yl)ethyl]benzamide;
  • N-(1-hydroxy-2-methylpropan-2-yl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-benzyl-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-(cyclopentylmethyl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(piperidin-1-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenoxyethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(propan-2-yloxy)ethyl]benzamide;
  • N-(2-hydroxy-2-methylpropyl)-4-[(imidazo[1,2-a]pyridin-6-yl carbamoyl)amino]benzamide;
  • N-[2-hydroxy-1-(4-methoxyphenyl)ethyl]-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(2-oxopyrrolidin-1-yl)ethyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydrofuran-2-ylmethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-propylbenzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(morpholin-4-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-phenylbenzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-methylbutyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydro-2H-pyran-4-ylmethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydro-2H-pyran-2-ylmethyl)benzamide;
  • N-[(1,1-dioxidotetrahydrothiophen-3-yl)methyl]-4-[(imidazo[1,2-a]pyridin-6-yl carbamoyl)amino]benzamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(tetrahydrofuran-3-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(morpholin-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(1-methylpiperidin-4-yl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 2-ethoxy-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(morpholin-4-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(2-methoxyethoxy)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3-methoxy-2-methylpropanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}butanamide;
  • 4,4,4-trifluoro-N-{4-[(imidazo[1,2-a]pyridin-6-yl carbamoyl)amino]phenyl}butanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}tetrahydro-2H-pyran-4-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-4-methylpentanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-1-methylpiperidine-4-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-1,4-dioxane-2-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 2[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide;
  • 2[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]butyl}piperidine-1-carboxylate;
  • 4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)benzamide;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}butyl)urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]butyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-{4-[1-(cyclopropylacetyl)piperidin-4-yl]butyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]butyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}butyl)urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro furan-3-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]butyl}urea;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 2-cyclopentyl-N-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxoethyl]phenyl}acetamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(morpholin-4-ylacetyl)amino]benzamide;
  • 4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-{4-[(cyclopentylacetyl)amino]benzyl}imidazo[1,2-a]pyridine-6-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(3-phenylpyrrolidin-1-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide;
  • 2-(1,3-dihydro-2H-isoindol-2-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(morpholin-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro furan-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro furan-2-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[3-(tetrahydrofuran-2-yl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluorocyclohexyl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)butyl]-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 2-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;


tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;

  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[2-oxo-4-(tetrahydrofuran-3-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(2-oxo-5-phenyl-1,3-oxazolidin-3-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methyl-1,3-thiazol-5-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methyl-1,3-thiazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(3-methyl-1,2-oxazol-5-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[3-(3-chloro-1,2-oxazol-5-yl)propanoyl](tetrahydro furan-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(3-methoxy-1,2-oxazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-{[3-(3,5-dimethyl-1,2-oxazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1-methyl-1H-pyrazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(4-methyl-1,3-thiazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-2-ylmethyl)(1H-tetrazol-5-ylacetyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1,2-oxazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(1,2-oxazol-3-ylacetyl)(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1,2-oxazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydrofuran-2-ylmethyl)[3-(1,3-thiazol-2-yl)propanoyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutanoyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydrofuran-3-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-3-ylmethyl)(tetrahydro-2H-pyran-4-ylcarbonyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydrofuran-3-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-3-ylcarbonyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydro-2H-pyran-4-ylcarbonyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(3-methoxypropanoyl)[(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydro furan-3-ylcarbonyl) [(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2R)-tetrahydrofuran-2-ylmethyl](tetrahydro-2H-pyran-4-ylcarbonyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(3-methoxypropanoyl)[(2S)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydro furan-3-ylcarbonyl)[(2S)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2S)-tetrahydrofuran-2-ylmethyl](tetrahydro-2H-pyran-4-ylcarbonyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydro-2H-pyran-4-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-({[2-(propan-2-yloxy)ethyl]carbamoyl}[(2R)-tetrahydrofuran-2-ylmethyl]amino)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl][(2S)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-({[2-(propan-2-yloxy)ethyl]carbamoyl}[(2S)-tetrahydrofuran-2-ylmethyl]amino)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-3-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • 2-[5-(4-chlorophenyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-[(1-butanoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(3-methoxy-2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropanoyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(cyclohexylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2R)-2-hydroxybutyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(1-methyl-1H-pyrazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,3-dimethyl-1H-pyrazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 2-{(4R)-4-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-{(4S)-4-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1-methyl-1H-pyrrol-2-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,5-dimethyl-1H-pyrazol-3-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-2-ylmethyl)(1,3-thiazol-4-ylacetyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(1,2-oxazol-3-ylacetyl)[(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(5-methyl-1,2-oxazol-3-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1,2-oxazol-5-yl)propanoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1,2-oxazol-4-yl)propanoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(2R)-tetrahydrofuran-2-ylmethyl](1,3-thiazol-4-ylacetyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,5-dimethyl-1H-pyrazol-3-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1-methyl-1H-pyrazol-4-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(1-methyl-1H-pyrazol-4-yl)acetyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1-methyl-1H-pyrrol-2-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • 2-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • tert-butyl {4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[3-(tetrahydrofuran-2-yl)propanoyl]amino}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide;
  • 4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(4-methylpentanoyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • 4-[(4-cyanobenzyl)(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 2-{5-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro furan-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3-hydroxy-3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 5-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]thiophene-2-carboxamide;
  • 1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 2-[(2S)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 5-[1-(cyclopropylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]thiophene-2-carboxamide;
  • 2-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(5S)-2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(5R)-2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methoxyacetyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[(4S)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 1-[4-(1-benzoylpiperidin-4-yl)butyl]-3-imidazo[1,2-a]pyridin-7-ylurea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(cyclohexylmethyl)-5-ethyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methoxy-3,3-dimethylcyclohexyl)methyl]-5-methyl-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide;
  • 3-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)propanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(propan-2-yloxy)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydrofuran-2-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-3-phenylpropanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide;
  • 3-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)propanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(propan-2-yloxy)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydrofuran-2-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3-phenylpropanamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate;
  • tert-butyl (3R)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate;
  • tert-butyl {2-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-(1-ethyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(1,1-dioxidotetrahydrothiophen-3-yl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-phenylthiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(methylsulfonyl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}pyrrolidine-1-carboxylate;
  • tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)pyrrolidine-1-carboxylate;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)biphenyl-2-sulfonamide;
  • 5-{1-[(2R)-2-hydroxypropyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-3-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-{2-fluoro-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3R)-tetrahydro furan-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • tert-butyl 4-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxo ethyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(propan-2-yloxy)phenyl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • tert-butyl 4-[4-(imidazo[1,2-a]pyridin-7-ylcarbamoyl)phenyl]piperidine-1-carboxylate;
  • tert-butyl 4-[4-(imidazo[1,2-a]pyridin-6-ylcarbamoyl)phenyl]piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(2-methylpropanoyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • 5-[3-(benzoylamino)oxetan-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(tetrahydrofuran-3-ylacetyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(pentanoylamino)oxetan-3-yl]thiophene-2-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3R)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2R)-tetrahydro furan-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}benzamide;
  • 5-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-3-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • 4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(3-methoxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(3-hydroxy-3-methylbutanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2-(4-benzoylpiperazin-1-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(propan-2-yl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(2-methoxyethyl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • 1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-phenyl-1,3-thiazole-5-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide;


tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)azetidine-1-carboxylate;

  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydro furan-3-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]benzamide;
  • 1-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydro furan-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydro furan-3-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 4-{[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]amino}-N-(tetrahydro-2H-pyran-2-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydro furan-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-6-yl)methyl]-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • 5-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxylate;
  • tert-butyl 4-hydroxy-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[5-(piperidin-1-ylcarbonyl)-1,3-thiazol-2-yl]urea;
  • 5-{3-hydroxy-1-[(2S)-2-methylbutanoyl]azetidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(3-{[(2S)-2-methylbutanoyl]amino}oxetan-3-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1-[1-(3-methylbutanoyl)piperidin-4-yl]-1H-pyrazole-3-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • 1-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(propan-2-yloxy)acetyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2R)-tetrahydro furan-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[1-(1,4-dioxan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)urea;
  • tert-butyl (3R)-3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}pyrrolidine-1-carboxylate;
  • 4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-[4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-{1-[(3,3-difluorocyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2R)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{4-[(propan-2-yloxy)acetyl]azetidin-3-yl}phenyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydro furan-2-ylcarbonyl]azetidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}urea;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[6-(morpholin-4-yl)pyridin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methyltetrahydro-2H-pyran-2-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylbutanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-{[(2S)-2-methylbutanoyl]amino}cyclobutyl)thiophene-2-carboxamide;
  • 5-[1-(benzoylamino)cyclobutyl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3,3,3-trifluoropropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(1-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}cyclobutyl)tetrahydro-2H-pyran-4-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}azetidine-1-carboxylate;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-phenoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)azetidin-3-yl]benzamide;
  • tert-butyl 4-{4-[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-phenoxyphenyl)urea;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohexylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • 4-(1-butanoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylpent-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyloxetan-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyanocyclopropyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopentylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-oxobutanoyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-propanoylpiperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 5-[4-hydroxy-1-(3-methylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[4-hydroxy-1-(2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)-4-hydroxypiperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylazetidin-3-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • tert-butyl 4-{4-[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 2-cyclopentyl-N-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • tert-butyl 4-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-1-ylcarbonyl)benzamide;
  • 4-[1-(ethylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)azetidin-3-yl]benzamide;
  • propan-2-yl 4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 2-methylpropyl 4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(2-cyano-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3R)-tetrahydrofuran-3-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}benzamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(ethylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)azetidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide;
  • 4-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-{(1R)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{(1R)-3-methyl-1-[(tetrahydrofuran-3-ylacetyl)amino]butyl}thiophene-2-carboxamide;
  • 5-{(1S)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1-phenylpiperidin-4-yl)-1,3-thiazole-5-carboxamide;
  • 1-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl]oxy)phenyl}urea;
  • 1-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(pyridin-2-yl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • 1-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(phenylacetyl)piperidin-4-yl]phenyl}urea;
  • 5-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 1-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,4-difluorobenzoyl)piperdin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]benzamide;
  • 4-{1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]furan-2-carboxamide;
  • 4-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • 5-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[4-(2-methylpropyl)phenyl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{1-[(2-methylpropyl)sulfonyl]pyrrolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(phenylsulfonyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidine-1-carboxylate;
  • 5-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-{1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2E)-2-methylpent-2-enoyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-{1-[(2,5-dimethylfuran-3-yl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propanoylpyrrolidin-3-yl)thiophene-2-carboxamide;
  • 5-{1-[(1-cyanocyclopropyl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-butanoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyrazin-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(phenylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • 2-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 5-[1-(2-fluorobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 2-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-[2-(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)ethyl]piperazine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • 4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutyl)-1H-pyrazol-5-yl]furan-2-carboxamide;
  • 5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(3-methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-methylbutanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(1-methylpiperidin-4-yl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}acetamide;
  • tert-butyl 4-{4-[(imidazo[1,2-b]pyridazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-b]pyridazin-6-ylmethyl)benzamide;
  • 5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(propan-2-ylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(phenylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}piperidine-1-carboxylate;
  • N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide;
  • 2-(imidazo[1,2-a]pyridin-6-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}acetamide;
  • N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2-methoxyphenyl)acetyl]amino}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(phenylacetyl)amino]benzamide;
  • 4-(benzoylamino)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 3,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 3,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 2,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 2-fluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-3-methoxybenzamide;
  • 4-{[(2-fluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-2-methoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • 4-(phenylsulfonyl)-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)benzamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tricyclo[3.3.1.1˜3,7˜]dec-1-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-oxatricyclo[3.3.1.1˜3,7˜]dec-1-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 4-{[(2,5-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(2,4-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 4-{[difluoro(phenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(2-methyl-2-phenylpropanoyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate;
  • N-[(3-chloroimidazo[1,2-a]pyrazin-6-yl)methyl]-4-[(cyclopentylacetyl)amino]benzamide;
  • N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • 2-(imidazo[1,2-a]pyridin-7-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}acetamide;
  • 1-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-methyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide;
  • 5-[1-benzyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • N-(2,5-difluorobenzyl)-N′-(imidazo[1,2-a]pyridin-7-ylmethyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(propan-2-yl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbut-2-enoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-fluoro-4-methoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopent-1-en-1-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-ethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxyphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2-acetylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(methoxymethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-phenylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[(2-methylpropyl)sulfonyl]acetyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-phenoxypropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-({[(1R,2S)-2-methylcyclohexyl]oxy}acetyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxyphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylbut-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-methylphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-(4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3-methylbut-2-enoyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopent-1-en-1-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,4-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,5-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-oxo-2,3-dihydro-1H-inden-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-2-methylbut-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(1H-indol-3-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(pyridin-2-yl)cyclopropyl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-dihydro-2H-chromen-6-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(cyclohexyloxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloropyridin-3-yl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2H-chromen-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxycyclohexyl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-1,3-benzoxazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyano cyclopentyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thieno[3,2-b]pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinolin-7-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(5,6,7,8-tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-7-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinoxalin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(2-methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(pyridin-2-yl)prop-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(8-methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methyl-4H-furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-8-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{1-[(4-cyanophenyl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[3-methyl-1-(prop-2-en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)tetrahydro-2H-pyran-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxy-6-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(4-{1-[(2S)-2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(pyridin-2-yl)cyclopropyl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,3-dihydro-1-benzofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxycyclohexyl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-1,3-benzoxazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1-cyanocyclopentyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(cinnolin-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinolin-7-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(5,6,7,8-tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-7-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinoxalin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(2-methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(pyridin-2-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-2,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(8-methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methyl-4H-furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2,3-dihydro-1-benzofuran-5-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-1-ethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-8-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(4-cyanophenyl)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[3-methyl-1-(prop-2-en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-{4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-methyl-5-(propan-2-yl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 1-(4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • tert-butyl 4-{3-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(piperidin-1-ylcarbonyl)piperidin-4-yl]benzamide;
  • 1-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(2-fluoro-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2-cyanobenzoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-N,N-dimethylpiperidine-1-carboxamide;
  • 1-{2-fluoro-4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-[(cyclopentylacetyl)amino]-N-[(7-fluoroimidazo[1,2-a]pyridin-6-yl)methyl]benzamide;
  • N-[(7-fluoroimidazo[1,2-a]pyridin-6-yl)methyl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • 5-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]acetyl}piperidin-4-yl)benzamide;
  • 4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-1-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxy-5-methylpyridin-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[4-(propan-2-yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-5-propyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2,3-dihydro-1-benzo furan-7-yl)carbonyl}piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-O-1,3-thiazol-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-(1-{[1-(difluoromethyl)-5-methyl-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazolo[1,5-a]pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)-1,3-oxazol-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-methylpyridin-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 1-(4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(thieno[3,2-b]furan-5-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxy-5-methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[4-(propan-2-yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-5-propyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(pyrazolo[1,5-a]pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(propan-2-yl)-1,3-oxazol-4-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-7-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxy-5-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • 4-(1-benzoylpiperidin-4-yl)-2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine;
  • 5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin-4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine; and pharmaceutically acceptable salts thereof.


Still another embodiment pertains to compounds of Formula (IA), selected from the group consisting of

  • 4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluoro-4-methoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2-acetylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(methoxymethyl)benzoyl]piperidin-4-yl}benzamide;
  • 4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide; N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxy-6-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide; and pharmaceutically acceptable salts thereof.


Another embodiment pertains to a composition for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic upus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said composition comprising an excipient and a therapeutically effective amount of a compound of Formula (IB), or pharmaceutically acceptable salts thereof.


Another embodiment pertains to a method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of Formula (IB), or pharmaceutically acceptable salts thereof.


Another embodiment pertains to a method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia or spleen cancer in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of Formula (IB), or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.







DETAILED DESCRIPTION OF THE INVENTION

This detailed description is intended only to acquaint others skilled in the art with Applicants' invention, its principles, and its practical application so that others skilled in the art may adapt and apply the invention in its numerous forms, as they may be best suited to the requirements of a particular use. This description and its specific examples are intended for purposes of illustration only. This invention, therefore, is not limited to the embodiments described in this patent application, and may be variously modified.


ABBREVIATIONS AND DEFINITIONS

Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. With reference to the use of the words “comprise” or “comprises” or “comprising” in this patent application (including the claims), Applicants note that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that Applicants intend each of those words to be so interpreted in construing this patent application, including the claims below. For a variable that occurs more than one time in any substituent or in the compound of the invention or any other formulae herein, its definition on each occurrence is independent of its definition at every other occurrence. Combinations of substituents are permissible only if such combinations result in stable compounds. Stable compounds are compounds which can be isolated in a useful degree of purity from a reaction mixture.


It is meant to be understood that proper valences are maintained for all combinations herein, that monovalent moieties having more than one atom are attached through their left ends, and that divalent moieties are drawn from left to right.


As used in the specification and the appended claims, unless specified to the contrary, the following terms have the meaning indicated:


The term “alkyl” (alone or in combination with another term(s)) means a straight- or branched-chain saturated hydrocarbyl substituent typically containing from 1 to about 10 carbon atoms; or in another embodiment, from 1 to about 8 carbon atoms; in another embodiment, from 1 to about 6 carbon atoms; and in another embodiment, from 1 to about 4 carbon atoms. Examples of such substituents include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, and hexyl and the like.


The term “alkenyl” (alone or in combination with another term(s)) means a straight- or branched-chain hydrocarbyl substituent containing one or more double bonds and typically from 2 to about 10 carbon atoms; or in another embodiment, from 2 to about 8 carbon atoms; in another embodiment, from 2 to about 6 carbon atoms; and in another embodiment, from 2 to about 4 carbon atoms. Examples of such substituents include ethenyl (vinyl), 2-propenyl, 3-propenyl, 1,4-pentadienyl, 1,4-butadienyl, 1-butenyl, 2-butenyl, and 3-butenyl and the like.


The term “alkynyl” (alone or in combination with another term(s)) means a straight- or branched-chain hydrocarbyl substituent containing one or more triple bonds and typically from 2 to about 10 carbon atoms; or in another embodiment, from 2 to about 8 carbon atoms; in another embodiment, from 2 to about 6 carbon atoms; and in another embodiment, from 2 to about 4 carbon atoms. Examples of such substituents include ethynyl, 2-propynyl, 3-propynyl, 2-butynyl, and 3-butynyl and the like.


The term “carbocyclyl” (alone or in combination with another term(s)) means a saturated cyclic (i.e., “cycloalkyl”), partially saturated cyclic (i.e., “cycloalkenyl”), or completely unsaturated (i.e., “aryl”) hydrocarbyl substituent containing from 3 to 14 carbon ring atoms (“ring atoms” are the atoms bound together to form the ring or rings of a cyclic substituent). A carbocyclyl may be a single-ring (monocyclic) or polycyclic ring structure.


A carbocyclyl may be a single ring structure, which typically contains from 3 to 8 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms. Examples of such single-ring carbocyclyls include cyclopropyl (cyclopropanyl), cyclobutyl (cyclobutanyl), cyclopentyl (cyclopentanyl), cyclopentenyl, cyclopentadienyl, cyclohexyl (cyclohexanyl), cyclohexenyl, cyclohexadienyl, and phenyl. A carbocyclyl may alternatively be polycyclic (i.e., may contain more than one ring). Examples of polycyclic carbocyclyls include bridged, fused, and spirocyclic carbocyclyls. In a spirocyclic carbocyclyl, one atom is common to two different rings. An example of a spirocyclic carbocyclyl is spiropentanyl. In a bridged carbocyclyl, the rings share at least two common non-adjacent atoms. Examples of bridged carbocyclyls include bicyclo[2.2.1]heptanyl, bicyclo[2.2.1]hept-2-enyl, and adamantanyl. In a fused-ring carbocyclyl system, two or more rings may be fused together, such that two rings share one common bond. Examples of two- or three-fused ring carbocyclyls include naphthalenyl, tetrahydronaphthalenyl (tetralinyl), indenyl, indanyl (dihydroindenyl), anthracenyl, phenanthrenyl, and decalinyl.


The term “cycloalkyl” (alone or in combination with another term(s)) means a saturated cyclic hydrocarbyl substituent containing from 3 to 14 carbon ring atoms. A cycloalkyl may be a single carbon ring, which typically contains from 3 to 8 carbon ring atoms and more typically from 3 to 6 ring atoms. Examples of single-ring cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. A cycloalkyl may alternatively be polycyclic or contain more than one ring. Examples of polycyclic cycloalkyls include bridged, fused, and spirocyclic carbocyclyls.


The term “aryl” (alone or in combination with another term(s)) means an aromatic carbocyclyl containing from 6 to 14 carbon ring atoms. An aryl may be monocyclic or polycyclic (i.e., may contain more than one ring). In the case of polycyclic aromatic rings, only one ring the polycyclic system is required to be unsaturated while the remaining ring(s) may be saturated, partially saturated or unsaturated. Examples of aryls include phenyl, naphthalenyl, indenyl, indanyl, and tetrahydronapthyl.


In some instances, the number of carbon atoms in a hydrocarbyl substituent (e.g., alkyl, alkenyl, alkynyl, or cycloalkyl) is indicated by the prefix “Cx-Cy-”, wherein x is the minimum and y is the maximum number of carbon atoms in the substituent. Thus, for example, “C1-C6-alkyl” refers to an alkyl substituent containing from 1 to 6 carbon atoms. Illustrating further, C3-C8-cycloalkyl means a saturated hydrocarbyl ring containing from 3 to 8 carbon ring atoms.


The term “hydrogen” (alone or in combination with another term(s)) means a hydrogen radical, and may be depicted as —H.


The term “hydroxy” (alone or in combination with another term(s)) means —OH.


The term “carboxy” (alone or in combination with another term(s)) means —C(O)—OH.


The term “amino” (alone or in combination with another term(s)) means —NH2.


The term “halogen” or “halo” (alone or in combination with another term(s)) means a fluorine radical (which may be depicted as —F), chlorine radical (which may be depicted as —Cl), bromine radical (which may be depicted as —Br), or iodine radical (which may be depicted as —I).


If a substituent is described as being “substituted”, a non-hydrogen radical is in the place of hydrogen radical on a carbon or nitrogen of the substituent. Thus, for example, a substituted alkyl substituent is an alkyl substituent in which at least one non-hydrogen radical is in the place of a hydrogen radical on the alkyl substituent. To illustrate, monofluoroalkyl is alkyl substituted with a fluoro radical, and difluoroalkyl is alkyl substituted with two fluoro radicals. It should be recognized that if there are more than one substitution on a substituent, each non-hydrogen radical may be identical or different (unless otherwise stated).


If a substituent is described as being “optionally substituted”, the substituent may be either (1) not substituted or (2) substituted. If a substituent is described as being optionally substituted with up to a particular number of non-hydrogen radicals, that substituent may be either (1) not substituted; or (2) substituted by up to that particular number of non-hydrogen radicals or by up to the maximum number of substitutable positions on the substituent, whichever is less. Thus, for example, if a substituent is described as a heteroaryl optionally substituted with up to 3 non-hydrogen radicals, then any heteroaryl with less than 3 substitutable positions would be optionally substituted by up to only as many non-hydrogen radicals as the heteroaryl has substitutable positions. To illustrate, tetrazolyl (which has only one substitutable position) would be optionally substituted with up to one non-hydrogen radical. To illustrate further, if an amino nitrogen is described as being optionally substituted with up to 2 non-hydrogen radicals, then a primary amino nitrogen will be optionally substituted with up to 2 non-hydrogen radicals, whereas a secondary amino nitrogen will be optionally substituted with up to only 1 non-hydrogen radical.


This patent application uses the terms “substituent” and “radical” interchangeably.


The prefix “halo” indicates that the substituent to which the prefix is attached is substituted with one or more independently selected halogen radicals. For example, haloalkyl means an alkyl substituent in which at least one hydrogen radical is replaced with a halogen radical. Examples of haloalkyls include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, and 1,1,1-trifluoroethyl. It should be recognized that if a substituent is substituted by more than one halogen radical, those halogen radicals may be identical or different (unless otherwise stated).


The prefix “perhalo” indicates that every hydrogen radical on the substituent to which the prefix is attached is replaced with independently selected halogen radicals, i.e., each hydrogen radical on the substituent is replaced with a halogen radical. If all the halogen radicals are identical, the prefix typically will identify the halogen radical. Thus, for example, the term “perfluoro” means that every hydrogen radical on the substituent to which the prefix is attached is substituted with a fluorine radical. To illustrate, the term “perfluoroalkyl” means an alkyl substituent wherein a fluorine radical is in the place of each hydrogen radical.


The term “carbonyl” (alone or in combination with another term(s)) means —C(O)—.


The term “aminocarbonyl” (alone or in combination with another term(s)) means —C(O)—NH2.


The term “oxo” (alone or in combination with another term(s)) means (═O).


The term “oxy” (alone or in combination with another term(s)) means an ether substituent, and may be depicted as —O—.


The term “alkylhydroxy” (alone or in combination with another term(s)) means alkyl-OH.


The term “alkylamino” (alone or in combination with another term(s)) means alkyl-NH2.


The term “alkyloxy” (alone or in combination with another term(s)) means an alkylether substituent, i.e., —O-alkyl. Examples of such a substituent include methoxy (—O—CH3), ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy.


The term “alkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl.


The term “aminoalkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl-NH2.


The term “alkyloxycarbonyl” (alone or in combination with another term(s)) means —C(O)—O-alkyl.


The term “carbocyclylcarbonyl” (alone or in combination with another term(s)) means —C(O)-carbocyclyl.


Similarly, the term “heterocyclylcarbonyl” (alone or in combination with another term(s)) means —C(O)-heterocyclyl.


The term “carbocyclylalkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl-carbocyclyl.


Similarly, the term “heterocyclylalkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl-heterocyclyl.


The term “carbocyclyloxycarbonyl” (alone or in combination with another term(s)) means —C(O)—O-carbocyclyl.


The term “carbocyclylalkyloxycarbonyl” (alone or in combination with another term(s)) means —C(O)—O-alkyl-carbocyclyl.


The term “thio” or “thia” (alone or in combination with another term(s)) means a thiaether substituent, i.e., an ether substituent wherein a divalent sulfur atom is in the place of the ether oxygen atom. Such a substituent may be depicted as —S—. This, for example, “alkyl-thio-alkyl” means alkyl-S-alkyl (alkyl-sulfanyl-alkyl).


The term “thiol” or “sulfhydryl” (alone or in combination with another term(s)) means a sulfhydryl substituent, and may be depicted as —SH.


The term “(thiocarbonyl)” (alone or in combination with another term(s)) means a carbonyl wherein the oxygen atom has been replaced with a sulfur. Such a substituent may be depicted as —C(S)—.


The term “sulfonyl” (alone or in combination with another term(s)) means —S(O)2—.


The term “aminosulfonyl” (alone or in combination with another term(s)) means —S(O)2—NH2.


The term “sulfinyl” or “sulfoxido” (alone or in combination with another term(s)) means —S(O)—.


The term “heterocyclyl” (alone or in combination with another term(s)) means a saturated (i.e., “heterocycloalkyl”), partially saturated (i.e., “heterocycloalkenyl”), or completely unsaturated (i.e., “heteroaryl”) ring structure containing a total of 3 to 14 ring atoms. At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur. A heterocyclyl may be a single-ring (mono cyclic) or polycyclic ring structure.


A heterocyclyl may be a single ring, which typically contains from 3 to 7 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms. Examples of single-ring heterocyclyls include 1,2,3,6-tetrahydropyridine, thiomorpholinyl, tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thiophenyl (thiofuranyl), dihydrothiophenyl, tetrahydrothiophenyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolyl, oxazolyl, oxazolidinyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl, thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl, thiodiazolyl, oxadiazolyl (including 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl (furazanyl), or 1,3,4-oxadiazolyl), oxatriazolyl (including 1,2,3,4-oxatriazolyl or 1,2,3,5-oxatriazolyl), dioxazolyl (including 1,2,3-dioxazolyl, 1,2,4-dioxazolyl, 1,3,2-dioxazolyl, or 1,3,4-dioxazolyl), oxathiazolyl, oxathiolyl, oxathiolanyl, pyranyl, dihydropyranyl, thiopyranyl, tetrahydrothiopyranyl, pyridinyl (azinyl), piperidinyl, diazinyl (including pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), or pyrazinyl (1,4-diazinyl)), piperazinyl, pyrrolidin-2-only, triazinyl (including 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,2,3-triazinyl)), oxazinyl (including 1,2-oxazinyl, 1,3-oxazinyl, or 1,4-oxazinyl)), oxathiazinyl (including 1,2,3-oxathiazinyl, 1,2,4-oxathiazinyl, 1,2,5-oxathiazinyl, or 1,2,6-oxathiazinyl)), oxadiazinyl (including 1,2,3-oxadiazinyl, 1,2,4-oxadiazinyl, 1,4,2-oxadiazinyl, or 1,3,5-oxadiazinyl)), morpholinyl, azepinyl, oxepinyl, thiepinyl, and diazepinyl.


A heterocyclyl may alternatively be polycyclic (i.e., may contain more than one ring). Examples of polycyclic heterocyclyls include bridged, fused, and spirocyclic heterocyclyls. In a spirocyclic heterocyclyl, one atom is common to two different rings. In a bridged heterocyclyl, the rings share at least two common non-adjacent atoms. In a fused-ring heterocyclyl, two or more rings may be fused together, such that two rings share one common bond. Examples of fused-ring heterocyclyls include hexahydro-furo[3,4-c]pyrrole, hexahydro-furo[3,4-b]pyrrole, octahydro-pyrrolo[3,4-b]pyridine, octahydro-pyrrolo[3,4-c]pyridine, (3aR,6aR)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole, (3aR,6aR)-octahydro-pyrrolo[3,4-b]pyrrole, 6-methyl-2,6-diaza-bicyclo[3.2.0]heptane, (3aS,6aR)-2-methyl-octahydro-pyrrolo[3,4-c]pyrrole, decahydro-[1,5]naphthyridine, 2,3-dihydrobenzofuranyl, 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, phthalazin-1(2H)-onyl, isoquinolinyl, isoquinolin-1(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-1(2H)-onyl, fluorophthalazin-1(2H)-onyl, (Z)-3H-benzo[d][1,2]diazepin-4(5H)-onyl, (trifluoromethyl)phthalazin-1(2H)-onyl, pyrrolo[1,2-d][1,2,4]triazin-1(2H)-onyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,3-dihydrobenzo[b][1,4]dioxinyl, 5,6,7,8-tetrahydrophthalazin-1(2H)-onyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, indolizinyl, pyranopyrrolyl, 4H-quinolizinyl, purinyl, naphthyridinyl, pyridopyridinyl (including pyrido[3,4-b]-pyridinyl, pyrido[3,2-b]-pyridinyl, or pyrido[4,3-b]-pyridinyl), and pteridinyl. Other examples of fused-ring heterocyclyls include benzo-fused heterocyclyls, such as benzimidazolyl, benzo[d][1,3]dioxolyl, indolyl, isoindolyl (isobenzazolyl, pseudoisoindolyl), indoleninyl (pseudoindolyl), isoindazolyl (benzpyrazolyl), benzazinyl (including quinolinyl (1-benzazinyl) or isoquinolinyl (2-benzazinyl)), phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl (including cinnolinyl (1,2-benzodiazinyl) or quinazolinyl (1,3-benzodiazinyl)), benzopyranyl (including chromanyl or isochromanyl), benzoxazinyl (including 1,3,2-benzoxazinyl, 1,4,2-benzoxazinyl, 2,3,1-benzoxazinyl, or 3,1,4-benzoxazinyl), and benzisoxazinyl (including 1,2-benzisoxazinyl or 1,4-benzisoxazinyl). Examples of spirocyclic heterocyclyls include 1,4-dioxa-8-azaspiro[4.5]decanyl.


The term “5-6 membered heteroaryl” (alone or in combination with another term(s)) means aromatic heterocyclyl containing a total of 5 to 6 ring atoms. At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.


The term “heterocycloalkyl” (alone or in combination with another term(s)) means a saturated heterocyclyl.


The term “heteroaryl” (alone or in combination with another term(s)) means an aromatic heterocyclyl containing from 5 to 14 ring atoms. A heteroaryl may be a single ring or 2 or 3 fused rings. Examples of heteroaryl substituents include 6-membered ring substituents such as pyridyl, pyrazyl, pyrimidinyl, pyridazinyl, and 1,3,5-, 1,2,4- or 1,2,3-triazinyl; 5-membered ring substituents such as imidazyl, furanyl, thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,3-, 1,2,4-, 1,2,5-, or 1,3,4-oxadiazolyl and isothiazolyl; 6/5-membered fused ring substituents such as benzothiofuranyl, benzisoxazolyl, benzoxazolyl, and purinyl; and 6/6-membered fused rings such as benzopyranyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, and benzoxazinyl.


A prefix attached to a multi-component substituent only applies to the first component. To illustrate, the term “alkylcycloalkyl” contains two components: alkyl and cycloalkyl. Thus, the C1-C6- prefix on C1-C6-alkylcycloalkyl means that the alkyl component of the alkylcycloalkyl contains from 1 to 6 carbon atoms; the C1-C6-prefix does not describe the cycloalkyl component. To illustrate further, the prefix “halo” on haloalkyloxyalkyl indicates that only the alkyloxy component of the alkyloxyalkyl substituent is substituted with one or more halogen radicals. If halogen substitution may alternatively or additionally occur on the alkyl component, the substituent would instead be described as “halogen-substituted alkyloxyalkyl” rather than “haloalkyloxyalkyl.” And finally, if the halogen substitution may only occur on the alkyl component, the substituent would instead be described as “alkyloxyhaloalkyl.”


The terms “treat”, “treating” and “treatment” refer to a method of alleviating or abrogating a disease and/or its attendant symptoms.


The terms “prevent”, “preventing” and “prevention” refer to a method of preventing the onset of a disease and/or its attendant symptoms or barring a subject from acquiring a disease. As used herein, “prevent”, “preventing” and “prevention” also include delaying the onset of a disease and/or its attendant symptoms and reducing a subject's risk of acquiring a disease.


The term “therapeutically effective amount” refers to that amount of the compound being administered sufficient to prevent development of or alleviate to some extent one or more of the symptoms of the condition or disorder being treated.


The term “modulate” refers to the ability of a compound to increase or decrease the function, or activity, of a kinase. “Modulation”, as used herein in its various forms, is intended to encompass antagonism, agonism, partial antagonism and/or partial agonism of the activity associated with kinase. Kinase inhibitors are compounds that, e.g., bind to, partially or totally block stimulation, decrease, prevent, delay activation, inactivate, desensitize, or down regulate signal transduction. Kinase activators are compounds that, e.g., bind to, stimulate, increase, open, activate, facilitate, enhance activation, sensitize or up regulate signal transduction.


The term “composition” as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By “pharmaceutically acceptable” it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.


The “subject” is defined herein to include animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In preferred embodiments, the subject is a human.


Isotope Enriched or Labeled Compounds


Compounds of the invention can exist in isotope-labeled or -enriched form containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number most abundantly found in nature. Isotopes can be radioactive or non-radioactive isotopes. Isotopes of atoms such as hydrogen, carbon, phosphorous, sulfur, fluorine, chlorine, and iodine include, but are not limited to, 2H, 3H, 13C, 14C, 15N, 18O, 32P, 35S, 18F, 36Cl and 125I. Compounds that contain other isotopes of these and/or other atoms are within the scope of this invention.


In another embodiment, the isotope-labeled compounds contain deuterium (2H), tritium (3H) or 14C isotopes. Isotope-labeled compounds of this invention can be prepared by the general methods well known to persons having ordinary skill in the art. Such isotope-labeled compounds can be conveniently prepared by carrying out the procedures disclosed in the Examples disclosed herein and Schemes by substituting a readily available isotope-labeled reagent for a non-labeled reagent. In some instances, compounds may be treated with isotope-labeled reagents to exchange a normal atom with its isotope, for example, hydrogen for deuterium can be exchanged by the action of a deuteric acid such as D2SO4/D2O. In addition to the above, relevant procedures and intermediates are disclosed, for instance, in Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3), 673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCT publications WO1997010223, WO2005099353, WO1995007271, WO2006008754; U.S. Pat. Nos. 7,538,189; 7,534,814; 7,531,685; 7,528,131; 7,521,421; 7,514,068; 7,511,013; and US Patent Application Publication Nos. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416; and 20090082471, the methods are hereby incorporated by reference.


The isotope-labeled compounds of the invention may be used as standards to determine the effectiveness in binding assays. Isotope containing compounds have been used in pharmaceutical research to investigate the in vivo metabolic fate of the compounds by evaluation of the mechanism of action and metabolic pathway of the nonisotope-labeled parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the design of safe, effective therapeutic drugs, either because the in vivo active compound administered to the patient or because the metabolites produced from the parent compound prove to be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut., 36(10):927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).


In addition, non-radio active isotope containing drugs, such as deuterated drugs called “heavy drugs,” can be used for the treatment of diseases and conditions related to NAMPT activity. Increasing the amount of an isotope present in a compound above its natural abundance is called enrichment. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol %. Replacement of up to about 15% of normal atom with a heavy isotope has been effected and maintained for a period of days to weeks in mammals, including rodents and dogs, with minimal observed adverse effects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci. 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201: 357). Acute replacement of as high as 15%-23% in human fluids with deuterium was found not to cause toxicity (Blagojevic N et al. in “Dosimetry & Treatment Planning for Neutron Capture Therapy”, Zamenhof R, Solares G and Harling O Eds. 1994. Advanced Medical Publishing, Madison Wis. pp. 125-134; Diabetes Metab. 23: 251 (1997)).


Stable isotope labeling of a drug can alter its physico-chemical properties such as pKa and lipid solubility. These effects and alterations can affect the pharmacodynamic response of the drug molecule if the isotopic substitution affects a region involved in a ligand-receptor interaction. While some of the physical properties of a stable isotope-labeled molecule are different from those of the unlabeled one, the chemical and biological properties are the same, with one important exception: because of the increased mass of the heavy isotope, any bond involving the heavy isotope and another atom will be stronger than the same bond between the light isotope and that atom. Accordingly, the incorporation of an isotope at a site of metabolism or enzymatic transformation will slow said reactions potentially altering the pharmacokinetic profile or efficacy relative to the non-isotopic compound.


Compounds


Suitable groups for X, R1, and Z in all Formulas are independently selected. The described embodiments of the present invention may be combined. Such combination is contemplated and within the scope of the present invention. For example, it is contemplated that embodiments for any of X, R1, and Z can be combined with embodiments defined for any other of X, R1, and Z.


Embodiments of Formula (I)


One embodiment, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (I)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3; and CH2NHC(O)R3; and


Z is CH or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is hydrogen;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3; and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl;


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


m is 4, 5, or 6; and


n is 1 or 2;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


In one embodiment of Formula (I), X is N or CY1. In another embodiment of Formula (I), X is N. In another embodiment of Formula (I), X is CY1.


In one embodiment of Formula (I), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (I), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (I), X is CY1; and Y1 is Cl. In another embodiment of Formula (I), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (I), Z is CH or N; R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is NHC(O)NH(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is CH2NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is NHC(O)(CH2)nR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is C(O)NH(CH2)nR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is NHC(O)(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is C(O)NH(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is CH2C(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH or N; R1 is CH2NHC(O)R3; and R2 is hydrogen.


In one embodiment of Formula (I), Z is CH; R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is NHC(O)NH(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is CH2NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is NHC(O)(CH2)nR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is C(O)NH(CH2)nR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is NHC(O)(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is C(O)NH(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is CH2C(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is CH; R1 is CH2NHC(O)R3; and R2 is hydrogen.


In one embodiment of Formula (I), Z is N; R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is NHC(O)NH(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is CH2NHC(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is NHC(O)R3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is NHC(O)(CH2)nR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is C(O)NH(CH2)nR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is NHC(O)(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is C(O)NH(CH2)mR3x; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is CH2C(O)NHR3; and R2 is hydrogen. In another embodiment of Formula (I), Z is N; R1 is CH2NHC(O)R3; and R2 is hydrogen.


In one embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is NHC(O)NHR3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is CH2NHC(O)NHR3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is NHC(O)R3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is NHC(O)(CH2)nR3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is C(O)NH(CH2)nR3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is NHC(O)(CH2)mR3x. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is C(O)NH(CH2)mR3x. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is CH2C(O)NHR3. In another embodiment of Formula (I), R1 is hydrogen; Z is CR2; and R2 is CH2NHC(O)R3.


In one embodiment of Formula (I), m is 4, 5, or 6. In another embodiment of Formula (I), m is 4. In another embodiment of Formula (I), m is 5. In another embodiment of Formula (I), m is 6.


In one embodiment of Formula (I), n is 1 or 2. In another embodiment of Formula (I), n is 1. In another embodiment of Formula (I), n is 2.


In one embodiment of Formula (I), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (I), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (I), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (I), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (I), R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocycyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R3x is heterocyclyl; wherein each R3x heterocycyl is substituted with C(O)R4, or CO(O)R4.


In one embodiment of Formula (I), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (I), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (I), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (I), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (I), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (I), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (I), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (I), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (I), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (I), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (I), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (I), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (I)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3; and CH2NHC(O)R3; and


Z is CH or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen F, Cl, Br, and I;


R1 is hydrogen;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, CH2C(O)NHR3; and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R3x is independently heterocyclyl; wherein each R3x heterocyclyl is substituted with one substituents independently selected from the group consisting of C(O)R4, CO(O)R4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl;


R11 at each occurrence, is alkyl;


m is 4, or 5; and


n is 1;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


Still another embodiment pertains to compounds having Formula (I), which includes Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (II)


In another aspect, the present invention provides compounds of Formula (II)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (II) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (II), X is N or CY1. In another embodiment of Formula (II), X is N. In another embodiment of Formula (II), X is CY1.


In one embodiment of Formula (II), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (II), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (II), X is CY1; and Y1 is Cl. In another embodiment of Formula (II), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (II), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (II), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (II), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (II), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (II), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (II), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (II), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (II), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (II), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (II), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (II), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (II), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (II), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (II), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (II), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (II), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (II), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (II), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (II), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (II), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (II), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (II)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (II), which includes Example 2; and pharmaceutically acceptable salts thereof.


Embodiments of Formula (III)


In another aspect, the present invention provides compounds of Formula (III)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described in Formula (I) herein.


One embodiment pertains to compounds of Formula (III) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (III), X is N or CY1. In another embodiment of Formula (III), X is N. In another embodiment of Formula (III), X is CY1.


In one embodiment of Formula (III), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (III), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (III), X is CY1; and Y1 is Cl. In another embodiment of Formula (III), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (III), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (III), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (III), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (III), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (III), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (III), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (III), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (III), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (III), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (III), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (III), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (III), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (III), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (III), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (III), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (III), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (III), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (III), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (III), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (III), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (III), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (III)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (III), which includes Examples 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 89, 106, 109, 110, 111, 112, 113, 396, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IV)


In another aspect, the present invention provides compounds of Formula (IV)




embedded image



and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (IV) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IV), X is N or CY1. In another embodiment of Formula (IV), X is N. In another embodiment of Formula (IV), X is CY1.


In one embodiment of Formula (IV), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IV), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IV), X is CY1; and Y1 is Cl. In another embodiment of Formula (IV), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IV), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IV), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IV), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IV), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IV), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IV), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IV), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (IV), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IV), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IV), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IV), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IV), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IV), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IV), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IV), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (IV), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11COR11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IV), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (IV), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IV), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (IV), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IV), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IV)




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X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IV), which includes Examples 118, 216, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 243, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 302, 303, 306, 307, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 364, 366, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 404, 407, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 438, 439, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 486, 487, 496, 564, 565, 673, 674, 675, 689, 690, 691, 692, 693, 694, 695, 696, 709, 710, 711, 712, 713, 714, 715, 716, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (V)


In another aspect, the present invention provides compounds of Formula (V)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (V) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl;


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (V), X is N or CY1. In another embodiment of Formula (V), X is N. In another embodiment of Formula (V), X is CY1.


In one embodiment of Formula (V), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (V), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (V), X is CY1; and Y1 is Cl. In another embodiment of Formula (V), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (V), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (V), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (V), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (V), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (V), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (V), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (V), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (V), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (V), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (V), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (V), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (V), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (V), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (V), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (V), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (V), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (V), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (V), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (V), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (V), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (V), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (V)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (V), which include Examples 59, 60, 274, 275, 276, 277, 278, 279, 360, 362, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VI)


In another aspect, the present invention provides compounds of Formula (VI)




embedded image



and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (VI) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VI), X is N or CY1. In another embodiment of Formula (VI), X is N. In another embodiment of Formula (VI), X is CY1.


In one embodiment of Formula (VI), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VI), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VI), X is CY1; and Y1 is Cl. In another embodiment of Formula (VI), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VI), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VI), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VI), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VI), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VI), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VI), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VI), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (VI), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VI), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VI), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VI), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VI), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VI), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VI), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VI), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (VI), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VI), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VI), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VI), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (VI), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VI), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VI)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VI), which includes Examples 57, 117, 121, 138, 174, 181, 182, 185, 187, 188, 192, 193, 194, 195, 196, 197, 198, 199, 202, 203, 204, 205, 207, 208, 209, 210, 211, 212, 213, 214, 217, 218, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 241, 242, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 271, 272, 273, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 304, 305, 308, 309, 310, 311, 312, 313, 315, 316, 317, 318, 319, 320, 321, 324, 325, 326, 327, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 361, 363, 365, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 393, 394, 395, 397, 399, 400, 401, 402, 403, 405, 406, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 436, 437, 440, 441, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 488, 489, 490, 492, 493, 494, 495, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 677, 682, 683, 684, 685, 686, 687, 688, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 717, 718, 731, 732, 733, 734, 735, 736, 737, 738, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 818, 821, 823, 824, 825, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VII)


In another aspect, the present invention provides compounds of Formula (VII)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (VII) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VII), X is N or CY1. In another embodiment of Formula (VII), X is N. In another embodiment of Formula (VII), X is CY1.


In one embodiment of Formula (VII), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VII), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VII), X is CY1; and Y1 is Cl. In another embodiment of Formula (VII), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VII), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VII), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VII), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VII), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VII), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VII), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VII), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (VII), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VII), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VII), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VII), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VII), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VII), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VII), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VII), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (VII), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VII), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VII), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VII), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (VII), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VII), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VII)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VII), which includes Examples 52, 55, 56, 61, 75, 77, 78, 79, 80, 81, 82, 83, 85, 86, 87, 88, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 108, 114, 115, 116, 119, 120, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 175, 176, 177, 178, 179, 180, 183, 184, 186, 189, 190, 191, 200, 201, 206, 215, 219, 240, 358, 359, 398, 462, 621, 622, 676, 810, 820, 822, 831, 832, 833, 834, 835, 836, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VIII)


In another aspect, the present invention provides compounds of Formula (VIII)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (VIII) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIII), X is N or CY1. In another embodiment of Formula (VIII), X is N. In another embodiment of Formula (VIII), X is CY1.


In one embodiment of Formula (VIII), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIII), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIII), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIII), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIII), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIII), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIII), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIII), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIII), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIII), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIII), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (VIII), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIII), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIII), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIII), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIII), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIII), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIII), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIII), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (VIII), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIII), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VIII), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIII), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (VIII), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIII), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIII)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VIII), which includes Example 322, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IX)


In another aspect, the present invention provides compounds of Formula (IX)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (IX) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl; and


R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent; and


when X is CY1 and Y1 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl.


In one embodiment of Formula (IX), X is N or CY1. In another embodiment of Formula (IX), X is N. In another embodiment of Formula (IX), X is CY1.


In one embodiment of Formula (IX), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IX), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IX), X is CY1; and Y1 is Cl. In another embodiment of Formula (IX), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IX), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IX), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IX), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IX), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IX), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IX), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IX), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, and OH.


In another embodiment of Formula (IX), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IX), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IX), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IX), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IX), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IX), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IX), R8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IX), R8 at each occurrence, is independently alkyl.


In one embodiment of Formula (IX), R9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IX), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (IX), R10 at each occurrence, is independently selected from the group consisting of haloalkyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IX), R10 at each occurrence, is independently haloalkyl or alkyl.


In one embodiment of Formula (IX), R11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IX), R11 at each occurrence, is independently alkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IX)




embedded image


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, substituent independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl and heterocyclyl is optionally substituted with one, or two substituents independently selected from the group consisting of R8, OR8, CNF, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R6 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, substituent independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of R11, OR11, CO(O)R11, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of haloalkyl, and alkyl; and


R11 at each occurrence, is alkyl;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent; and


when X is CY1 and Y1 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl.


Still another embodiment pertains to compounds having Formula (IX), which includes Examples 53, 54, 76, 314, 323, 491, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IA)


One embodiment, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IA)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


Z is CH, C—F, C—Cl, C—Br, C—I or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is hydrogen, F, Cl, Br, or I;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I;


R11 at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


m is 4, 5, or 6; and


n is 1 or 2;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


In one embodiment of Formula (IA), X is N or CY1. In another embodiment of Formula (IA), X is N. In another embodiment of Formula (IA), X is CY1.


In one embodiment of Formula (IA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IA), X is CY1; and Y1 is Cl. In another embodiment of Formula (IA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IA), Z is CH, C—F, C—Cl, C—Br, C—I or N; and R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IA), Z is CH or N; and R1 is NHC(O)NHR3. In another embodiment of Formula (IA), Z is CH or N; and R1 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IA), Z is CH or N; and R1 is CH2NHC(O)NHR3. In another embodiment of Formula (IA), Z is CH or N; and R1 is NHC(O)R3. In another embodiment of Formula (IA), Z is CH or N; and R1 is NHC(O)(CH2)nR3. In another embodiment of Formula (IA), Z is CH or N; and R1 is C(O)NH(CH2)nR3. In another embodiment of Formula (IA), Z is CH or N; and R1 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IA), Z is CH or N; and R1 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IA), Z is CH or N; and R1 is CH2C(O)NHR3. In another embodiment of Formula (IA), Z is CH or N; and R1 is CH2NHC(O)R3.


In one embodiment of Formula (IA), Z is CH; and R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IA), Z is CH; and R1 is NHC(O)NHR3. In another embodiment of Formula (IA), Z is CH; and R1 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IA), Z is CH; and R1 is CH2NHC(O)NHR3. In another embodiment of Formula (IA), Z is CH; and R1 is NHC(O)R3. In another embodiment of Formula (IA), Z is CH; and R1 is NHC(O)(CH2)nR3. In another embodiment of Formula (IA), Z is CH; and R1 is C(O)NH(CH2)nR3. In another embodiment of Formula (IA), Z is CH; and R1 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IA), Z is CH; and R1 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IA), Z is CH; and R1 is CH2C(O)NHR3. In another embodiment of Formula (IA), Z is CH; and R1 is CH2NHC(O)R3.


In one embodiment of Formula (IA), Z is N; and R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IA), Z is N; and R1 is NHC(O)NHR3. In another embodiment of Formula (IA), Z is N; and R1 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IA), Z is N; and R1 is CH2NHC(O)NHR3. In another embodiment of Formula (IA), Z is N; and R1 is NHC(O)R3. In another embodiment of Formula (IA), Z is N; and R1 is NHC(O)(CH2)nR3. In another embodiment of Formula (IA), Z is N; and R1 is C(O)NH(CH2)nR3. In another embodiment of Formula (IA), Z is N; and R1 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IA), Z is N; and R1 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IA), Z is N; and R1 is CH2C(O)NHR3. In another embodiment of Formula (IA), Z is N; and R1 is CH2NHC(O)R3.


In one embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is NHC(O)NHR3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is CH2NHC(O)NHR3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is NHC(O)R3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is NHC(O)(CH2)nR3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is C(O)NH(CH2)nR3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is CH2C(O)NHR3. In another embodiment of Formula (IA), R1 is hydrogen; Z is CR2; and R2 is CH2NHC(O)R3.


In one embodiment of Formula (IA), m is 4, 5, or 6. In another embodiment of Formula (IA), m is 4. In another embodiment of Formula (IA), m is 5. In another embodiment of Formula (IA), m is 6.


In one embodiment of Formula (IA), n is 1 or 2. In another embodiment of Formula (IA), n is 1. In another embodiment of Formula (IA), n is 2.


In one embodiment of Formula (IA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, SO2R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, SO2R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IA), R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocycyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R3x is heterocyclyl; wherein each R3x heterocycyl is substituted with C(O)R4, or CO(O)R4.


In one embodiment of Formula (IA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R and Cl.


In one embodiment of Formula (IA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IA), R10 at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IA), R11, at each occurrence, is independently alkyl.


In another embodiment of Formula (IA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IA)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


Z is CH, C—F, or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, and Cl;


R1 is hydrogen;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, CH2C(O)NHR3, and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R3x is heterocyclyl; wherein the R3x heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of C(O)R4, CO(O)R4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F;


R11 at each occurrence, is independently cycloalkyl or alkyl;


m is 4, or 5; and


n is 1;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


Still another embodiment pertains to compounds having Formula (IA), which includes Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1027, 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035, 1036, 1037, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048, 1049, 1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077, 1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115, 1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125, 1126, 1127, 1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1151, 1152, 1153, 437, 508, 513, 516, 527, 529, 699, 915, 919, 923, 924, 925, 927, 934, 937, 985, 996, 999, 1009, 1095, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IIA)


In another aspect, the present invention provides compounds of Formula (IIA)




embedded image



and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IA).


One embodiment pertains to compounds of Formula (IIA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IIA), X is N or CY1. In another embodiment of Formula (IIA), X is N. In another embodiment of Formula (IIA), X is CY1.


In one embodiment of Formula (IIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IIA), X is CY1; and Y1 is Cl. In another embodiment of Formula (IIA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IIA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IIA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IIA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IIA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IIA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (IIA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IIA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IIA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IIA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IIA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIA)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IIA), which includes Example 2; and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IIIA)


In another aspect, the present invention provides compounds of Formula (IIIA)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described in Formula (IA) herein.


One embodiment pertains to compounds of Formula (IIIA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IIIA), X is N or CY1. In another embodiment of Formula (IIIA), X is N. In another embodiment of Formula (IIIA), X is CY1.


In one embodiment of Formula (IIIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IIIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IIIA), X is CY1; and Y1 is Cl. In another embodiment of Formula (IIIA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IIIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIIA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IIIA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IIIA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IIIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IIIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IIIA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IIIA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IIIA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IIIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (IIIA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IIIA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IIIA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IIIA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IIIA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIIA)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IIIA), which includes 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 89, 106, 109, 110, 111, 112, 113, 396, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IVA)


In another aspect, the present invention provides compounds of Formula (IVA)




embedded image



and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IA).


One embodiment pertains to compounds of Formula (IVA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IVA), X is N or CY1. In another embodiment of Formula (IVA), X is N. In another embodiment of Formula (IVA), X is CY1.


In one embodiment of Formula (IVA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IVA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IVA), X is CY1; and Y1 is Cl. In another embodiment of Formula (IVA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IVA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IVA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IVA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IVA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IVA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IVA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IVA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IVA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IVA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IVA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IVA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IVA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (IVA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IVA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IVA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IVA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IVA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IVA)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IVA), which includes Examples 118, 216, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 243, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 302, 303, 306, 307, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 364, 366, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 404, 407, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 438, 439, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 486, 487, 496, 564, 565, 673, 674, 675, 689, 690, 691, 692, 693, 694, 695, 696, 709, 710, 711, 712, 713, 714, 715, 716, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 912, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1027, 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035, 1036, 1037, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048, 1049, 1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059, 1060, 1065, 1066, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1078, 1121, 1122, 1123, 1124, 1125, 1126, 1127, 1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1151, 1152, 1153, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VA)


In another aspect, the present invention provides compounds of Formula (VA)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IA).


One embodiment pertains to compounds of Formula (VA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VA), X is N or CY1. In another embodiment of Formula (VA), X is N. In another embodiment of Formula (VA), X is CY1.


In one embodiment of Formula (VA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VA), X is CY1; and Y1 is Cl. In another embodiment of Formula (VA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VA)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VA), which includes 59, 60, 274, 275, 276, 277, 278, 279, 360, 362, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VIA)


In another aspect, the present invention provides compounds of Formula (VIA)




embedded image



and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IA).


One embodiment pertains to compounds of Formula (VIA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIA), X is N or CY1. In another embodiment of Formula (VIA), X is N. In another embodiment of Formula (VIA), X is CY1.


In one embodiment of Formula (VIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIA), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VIA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VIA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VIA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VIA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIA)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VIA), which includes Examples 57, 117, 121, 138, 174, 181, 182, 185, 187, 188, 192, 193, 194, 195, 196, 197, 198, 199, 202, 203, 204, 205, 207, 208, 209, 210, 211, 212, 213, 214, 217, 218, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 241, 242, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 271, 272, 273, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 304, 305, 308, 309, 310, 311, 312, 313, 315, 316, 317, 318, 319, 320, 321, 324, 325, 326, 327, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 361, 363, 365, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 393, 394, 395, 397, 399, 400, 401, 402, 403, 405, 406, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 436, 437, 440, 441, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 488, 489, 490, 492, 493, 494, 495, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 677, 682, 683, 684, 685, 686, 687, 688, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 717, 718, 731, 732, 733, 734, 735, 736, 737, 738, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 818, 821, 823, 824, 825, 857, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 895, 896, 899, 906, 907, 909, 910, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1061, 1062, 1063, 1064, 1068, 1077, 1082, 1083, 1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115, 1116, 1117, 1118, 1119, 1120, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VILA)


In another aspect, the present invention provides compounds of Formula (VILA)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IA).


One embodiment pertains to compounds of Formula (VIIA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIIA), X is N or CY1. In another embodiment of Formula (VIIA), X is N. In another embodiment of Formula (VIIA), X is CY1.


In one embodiment of Formula (VIIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIIA), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIIA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIIA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIIA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VIIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIIA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIIA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VIIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VIIA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VIIA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VIIA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIIA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VIIA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIIA)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VILA), which includes Examples 52, 55, 56, 61, 75, 77, 78, 79, 80, 81, 82, 83, 85, 86, 87, 88, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 108, 114, 115, 116, 119, 120, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 175, 176, 177, 178, 179, 180, 183, 184, 186, 189, 190, 191, 200, 201, 206, 215, 219, 240, 358, 359, 398, 462, 621, 622, 676, 810, 820, 822, 831, 832, 833, 834, 835, 836, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 859, 860, 882, 898, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (VIIIA)


In another aspect, the present invention provides compounds of Formula (VIIIA)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (VIIIA) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIIIA), X is N or CY1. In another embodiment of Formula (VIIIA), X is N. In another embodiment of Formula (VIIIA), X is CY1.


In one embodiment of Formula (VIIIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIIIA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIIIA), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIIIA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIIIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIIA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIIIA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VIIIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIIA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIIIA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIIIA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VIIIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (VIIIA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VIIIA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VIIIA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIIIA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VIIIA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIIIA)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VIIIA), which includes Examples 322; and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IXA)


In another aspect, the present invention provides compounds of Formula (IXA)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (IX) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent; and


when X is CY1 and Y1 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl.


In one embodiment of Formula (IXA), X is N or CY1. In another embodiment of Formula (IXA), X is N. In another embodiment of Formula (IXA), X is CY1.


In one embodiment of Formula (IXA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IXA), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IXA), X is CY1; and Y1 is Cl. In another embodiment of Formula (IXA), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IXA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXA), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IXA), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IXA), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IXA), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IXA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IXA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IXA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IXA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IXA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IXA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IXA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IXA), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (IXA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IXA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IXA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IXA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IXA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IXA)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent; and


when X is CY1 and Y1 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl.


Still another embodiment pertains to compounds having Formula (IXA), which includes Examples 53, 54, 76, 314, 323, 491, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (XA)


In another aspect, the present invention provides compounds of Formula (XA)




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and pharmaceutically acceptable salts thereof; wherein R4 is as described herein for Formula (IA).


One embodiment pertains to compounds of Formula (XA) or pharmaceutically acceptable salts thereof;


wherein


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I; and


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl.


In one embodiment of Formula (XA), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XA), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (XA), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XA), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (XA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XA), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (XA), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XA), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (XA), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (XA), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (XA), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (XA), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, and F.


In one embodiment of Formula (XA), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (XA), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (XA), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl. In another embodiment of Formula (XA), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (XA), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (XA)




embedded image



wherein


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl.


Still another embodiment pertains to compounds having Formula (XA), which includes Examples 217, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 298, 301, 308, 309, 310, 311, 312, 313, 315, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 402, 437, 440, 441, 484, 488, 490, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 547, 548, 549, 550, 551, 552, 557, 562, 567, 568, 569, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 682, 683, 684, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 731, 732, 733, 737, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1061, 1062, 1063, 1064, 1068, 1077, 1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115, 1116, 1117, 1118, 1119, 1120, and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IB)


One embodiment, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


Z is CH, C—F, C—Cl, C—Br, C—I or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R1 is hydrogen, F, Cl, Br, or I;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I;


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


m is 4, 5, or 6; and


n is 1 or 2;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)nR3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


In one embodiment of Formula (IB), X is N or CY1. In another embodiment of Formula (IB), X is N. In another embodiment of Formula (IB), X is CY1.


In one embodiment of Formula (IB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IB), X is CY1; and Y1 is Cl. In another embodiment of Formula (IB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IB), Z is CH, C—F, C—Cl, C—Br, C—I or N; and R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IB), Z is CH or N; and R1 is NHC(O)NHR3. In another embodiment of Formula (IB), Z is CH or N; and R1 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IB), Z is CH or N; and R1 is CH2NHC(O)NHR3. In another embodiment of Formula (IB), Z is CH or N; and R1 is NHC(O)R3. In another embodiment of Formula (IB), Z is CH or N; and R1 is NHC(O)(CH2)nR3. In another embodiment of Formula (IB), Z is CH or N; and R1 is C(O)NH(CH2)nR3. In another embodiment of Formula (IB), Z is CH or N; and R1 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IB), Z is CH or N; and R1 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IB), Z is CH or N; and R1 is CH2C(O)NHR3. In another embodiment of Formula (IB), Z is CH or N; and R1 is CH2NHC(O)R3.


In one embodiment of Formula (IB), Z is CH; and R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IB), Z is CH; and R1 is NHC(O)NHR3. In another embodiment of Formula (IB), Z is CH; and R1 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IB), Z is CH; and R1 is CH2NHC(O)NHR3. In another embodiment of Formula (IB), Z is CH; and R1 is NHC(O)R3. In another embodiment of Formula (IB), Z is CH; and R1 is NHC(O)(CH2)nR3. In another embodiment of Formula (IB), Z is CH; and R1 is C(O)NH(CH2)nR3. In another embodiment of Formula (IB), Z is CH; and R1 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IB), Z is CH; and R1 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IB), Z is CH; and R1 is CH2C(O)NHR3. In another embodiment of Formula (IB), Z is CH; and R1 is CH2NHC(O)R3.


In one embodiment of Formula (IB), Z is N; and R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IB), Z is N; and R1 is NHC(O)NHR3. In another embodiment of Formula (IB), Z is N; and R1 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IB), Z is N; and R1 is CH2NHC(O)NHR3. In another embodiment of Formula (IB), Z is N; and R1 is NHC(O)R3. In another embodiment of Formula (IB), Z is N; and R1 is NHC(O)(CH2)nR3. In another embodiment of Formula (IB), Z is N; and R1 is C(O)NH(CH2)nR3. In another embodiment of Formula (IB), Z is N; and R1 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IB), Z is N; and R1 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IB), Z is N; and R1 is CH2C(O)NHR3. In another embodiment of Formula (IB), Z is N; and R1 is CH2NHC(O)R3.


In one embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is NHC(O)NHR3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is NHC(O)NH(CH2)mR3x. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is CH2NHC(O)NHR3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is NHC(O)R3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is NHC(O)(CH2)nR3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is C(O)NH(CH2)R3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is NHC(O)(CH2)mR3x. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is C(O)NH(CH2)mR3x. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is CH2C(O)NHR3. In another embodiment of Formula (IB), R1 is hydrogen; Z is CR2; and R2 is CH2NHC(O)R3.


In one embodiment of Formula (IB), m is 4, 5, or 6. In another embodiment of Formula (IB), m is 4. In another embodiment of Formula (IB), m is 5. In another embodiment of Formula (IB), m is 6.


In one embodiment of Formula (IB), n is 1 or 2. In another embodiment of Formula (IB), n is 1. In another embodiment of Formula (IB), n is 2.


In one embodiment of Formula (IB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, SO2R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, SO2R4, OR4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IB), R3x is independently selected from the group consisting of phenyl and heterocyclyl; wherein each R3x phenyl and heterocycyl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R3x is heterocyclyl; wherein each R3x heterocycyl is substituted with C(O)R4, or CO(O)R4.


In one embodiment of Formula (IB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, and Cl.


In one embodiment of Formula (IB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IB), R10 at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (IB), R11, at each occurrence, is independently alkyl.


In another embodiment of Formula (IB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R1 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, NHC(O)(CH2)nR3, C(O)NH(CH2)nR3, NHC(O)(CH2)mR3x, C(O)NH(CH2)mR3x, CH2C(O)NHR3, and CH2NHC(O)R3; and


Z is CH, C—F, or N; or


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, and Cl;


R1 is hydrogen;


Z is CR2; and


R2 is independently selected from the group consisting of NHC(O)NHR3, NHC(O)NH(CH2)mR3x, CH2NHC(O)NHR3, NHC(O)R3, CH2C(O)NHR3, and CH2NHC(O)R3; and


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R3x is heterocyclyl; wherein the R3x heterocyclyl is substituted with one, two, three or four substituents independently selected from the group consisting of C(O)R4, CO(O)R4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10 at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F;


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


m is 4, or 5; and


n is 1;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent;


when X is CY1 and Y1 is hydrogen; R1 is NHC(O)R3; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)R3; n is 1; R2 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenylmethoxy or 3-fluorophenoxy;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)R3; n is 1; R2 is hydrogen; and R3 is furanyl; the R3 furanyl is not substituted with benzyl, or 3-fluorophenyl methyl;


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)R3; n is 1; R2 is hydrogen; and R3 is thienyl; the R3 thienyl is not substituted with phenoxy, 3-fluorophenoxy, or 3-chlorophenoxy; and


when X is CY1 and Y1 is hydrogen; R1 is C(O)NH(CH2)R3; n is 1; R2 is hydrogen; and R3 is R3 phenyl; the phenyl is not substituted at the para position with SO2R4 or SO2NHR4.


Still another embodiment pertains to compounds having Formula (IB), which includes

  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-7-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenylethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(morpholin-4-yl)ethyl]benzamide;
  • N-(1-hydroxy-2-methylpropan-2-yl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-benzyl-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-(cyclopentylmethyl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(piperidin-1-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenoxyethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(propan-2-yloxy)ethyl]benzamide;
  • N-(2-hydroxy-2-methylpropyl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-[2-hydroxy-1-(4-methoxyphenyl)ethyl]-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(2-oxopyrrolidin-1-yl)ethyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydrofuran-2-ylmethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-propylbenzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(morpholin-4-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-phenylbenzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-methylbutyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydro-2H-pyran-4-ylmethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydro-2H-pyran-2-ylmethyl)benzamide;
  • N-[(1,1-dioxidotetrahydrothiophen-3-yl)methyl]-4-[(imidazo[1,2-a]pyridin-6-yl carbamoyl)amino]benzamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(tetrahydrofuran-3-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(morpholin-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(1-methylpiperidin-4-yl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 2-ethoxy-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(morpholin-4-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(2-methoxyethoxy)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3-methoxy-2-methylpropanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}butanamide;
  • 4,4,4-trifluoro-N-{4-[(imidazo[1,2-a]pyridin-6-yl carbamoyl)amino]phenyl}butanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}tetrahydro-2H-pyran-4-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-4-methylpentanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-1-methylpiperidine-4-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-1,4-dioxane-2-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 2[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]butyl}piperidine-1-carboxylate;
  • 4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)benzamide;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}butyl)urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]butyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-{4-[1-(cyclopropylacetyl)piperidin-4-yl]butyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]butyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}butyl)urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro furan-3-ylacetyl)piperidin-4-yl]butyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]butyl}urea;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 2-cyclopentyl-N-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxoethyl]phenyl}acetamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(morpholin-4-ylacetyl)amino]benzamide;
  • 4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-{4-[(cyclopentylacetyl)amino]benzyl}imidazo[1,2-a]pyridine-6-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(3-phenylpyrrolidin-1-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide;
  • 2-(1,3-dihydro-2H-isoindol-2-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(morpholin-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-2-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[3-(tetrahydrofuran-2-yl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluorocyclohexyl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)butyl]-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 2-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[2-oxo-4-(tetrahydrofuran-3-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydro furan-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(2-oxo-5-phenyl-1,3-oxazolidin-3-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methyl-1,3-thiazol-5-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methyl-1,3-thiazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(3-methyl-1,2-oxazol-5-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[3-(3-chloro-1,2-oxazol-5-yl)propanoyl](tetrahydro furan-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(3-methoxy-1,2-oxazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-{[3-(3,5-dimethyl-1,2-oxazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1-methyl-1H-pyrazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(4-methyl-1,3-thiazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-2-ylmethyl)(1H-tetrazol-5-ylacetyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1,2-oxazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(1,2-oxazol-3-ylacetyl)(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1,2-oxazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydrofuran-2-ylmethyl) [3-(1,3-thiazol-2-yl)propanoyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutanoyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydro furan-3-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-3-ylmethyl)(tetrahydro-2H-pyran-4-ylcarbonyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydrofuran-3-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-3-ylcarbonyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydro-2H-pyran-4-ylcarbonyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(3-methoxypropanoyl)[(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydro furan-3-ylcarbonyl) [(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2R)-tetrahydrofuran-2-ylmethyl](tetrahydro-2H-pyran-4-ylcarbonyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(3-methoxypropanoyl)[(2S)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydrofuran-3-ylcarbonyl)[(2S)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2S)-tetrahydrofuran-2-ylmethyl](tetrahydro-2H-pyran-4-ylcarbonyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydro-2H-pyran-4-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[2-(propan-2-yloxy)ethyl]carbamoyl}[(2R)-tetrahydrofuran-2-ylmethyl]amino)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl][(2S)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[2-(propan-2-yloxy)ethyl]carbamoyl}[(2S)-tetrahydrofuran-2-ylmethyl]amino)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-3-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • 2-[5-(4-chlorophenyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-[(1-butanoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(3-methoxy-2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropanoyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(cyclohexylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2R)-2-hydroxybutyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(1-methyl-1H-pyrazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,3-dimethyl-1H-pyrazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 2-{(4R)-4-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-{(4S)-4-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1-methyl-1H-pyrrol-2-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,5-dimethyl-1H-pyrazol-3-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydrofuran-2-ylmethyl)(1,3-thiazol-4-ylacetyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(1,2-oxazol-3-ylacetyl)[(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(5-methyl-1,2-oxazol-3-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1,2-oxazol-5-yl)propanoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1,2-oxazol-4-yl)propanoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(2R)-tetrahydrofuran-2-ylmethyl](1,3-thiazol-4-ylacetyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,5-dimethyl-1H-pyrazol-3-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1-methyl-1H-pyrazol-4-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(1-methyl-1H-pyrazol-4-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1-methyl-1H-pyrrol-2-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • 2-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • tert-butyl {4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydro furan-2-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[3-(tetrahydrofuran-2-yl)propanoyl]amino}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide;
  • 4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(4-methylpentanoyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • 4-[(4-cyanobenzyl)(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 2-{5-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro furan-2-yl carbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3-hydroxy-3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 5-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]thiophene-2-carboxamide;
  • 1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 2-[(2S)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 5-[1-(cyclopropylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]thiophene-2-carboxamide;
  • 2-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(5S)-2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(5R)-2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methoxyacetyl)piperdin-4-yl]thiophene-2-carboxamide;
  • 5-(1-acetylpiperdin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[(4S)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 1-[4-(1-benzoylpiperidin-4-yl)butyl]-3-imidazo[1,2-a]pyridin-7-ylurea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(cyclohexylmethyl)-5-ethyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methoxy-3,3-dimethylcyclohexyl)methyl]-5-methyl-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide;
  • 3-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)propanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(propan-2-yloxy)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydrofuran-2-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-3-phenylpropanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide;
  • 3-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)propanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(propan-2-yloxy)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydrofuran-2-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3-phenylpropanamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate;
  • tert-butyl (3R)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate;
  • tert-butyl {2-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-(1-ethyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(1,1-dioxidotetrahydrothiophen-3-yl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-phenylthiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(methylsulfonyl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}pyrrolidine-1-carboxylate;
  • tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)pyrrolidine-1-carboxylate;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)biphenyl-2-sulfonamide;
  • 5-{1-[(2R)-2-hydroxypropyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-3-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-{2-fluoro-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydro furan-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • tert-butyl 4-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxo ethyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(propan-2-yloxy)phenyl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • tert-butyl 4-[4-(imidazo[1,2-a]pyridin-7-ylcarbamoyl)phenyl]piperidine-1-carboxylate;
  • tert-butyl 4-[4-(imidazo[1,2-a]pyridin-6-ylcarbamoyl)phenyl]piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(2-methylpropanoyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • 5-[3-(benzoylamino)oxetan-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(tetrahydrofuran-3-ylacetyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(pentanoylamino)oxetan-3-yl]thiophene-2-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3R)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}benzamide;
  • 5-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-3-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • 4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(3-methoxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(3-hydroxy-3-methylbutanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2-(4-benzoylpiperazin-1-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(propan-2-yl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(2-methoxyethyl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • 1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-phenyl-1,3-thiazole-5-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide;
  • tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}-phenyl)azetidine-1-carboxylate;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydro furan-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]benzamide;
  • 1-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydro furan-3-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 4-{[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]amino}-N-(tetrahydro-2H-pyran-2-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydro furan-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-6-yl)methyl]-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • 5-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxylate;
  • tert-butyl 4-hydroxy-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[5-(piperidin-1-ylcarbonyl)-1,3-thiazol-2-yl]urea;
  • 5-{3-hydroxy-1-[(2S)-2-methylbutanoyl]azetidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(3-{[(2S)-2-methylbutanoyl]amino}oxetan-3-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1-[1-(3-methylbutanoyl)piperidin-4-yl]-1H-pyrazole-3-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • 1-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(propan-2-yloxy)acetyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2R)-tetrahydro furan-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[1-(1,4-dioxan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)urea;
  • tert-butyl (3R)-3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}pyrrolidine-1-carboxylate;
  • 4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-[4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-{1-[(3,3-difluorocyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2R)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(propan-2-yloxy)acetyl]azetidin-3-yl}phenyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydro furan-2-ylcarbonyl]azetidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}urea;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[6-(morpholin-4-yl)pyridin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methyltetrahydro-2H-pyran-2-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylbutanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-{[(2S)-2-methylbutanoyl]amino}cyclobutyl)thiophene-2-carboxamide;
  • 5-[1-(benzoylamino)cyclobutyl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3,3,3-trifluoropropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(1-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}cyclobutyl)tetrahydro-2H-pyran-4-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}azetidine-1-carboxylate;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-phenoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)azetidin-3-yl]benzamide;
  • tert-butyl 4-{4-[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-phenoxyphenyl)urea;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohexylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • 4-(1-butanoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylpent-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyloxetan-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyanocyclopropyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopentylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-oxobutanoyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-propanoylpiperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 5-[4-hydroxy-1-(3-methylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[4-hydroxy-1-(2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)-4-hydroxypiperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylazetidin-3-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • tert-butyl 4-{4-[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 2-cyclopentyl-N-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • tert-butyl 4-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-1-ylcarbonyl)benzamide;
  • 4-[1-(ethylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)azetidin-3-yl]benzamide;
  • propan-2-yl-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 2-methylpropyl 4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(2-cyano-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3R)-tetrahydrofuran-3-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}benzamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(ethylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)azetidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide;
  • 4-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-{(1R)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{(1R)-3-methyl-1-[(tetrahydrofuran-3-ylacetyl)amino]butyl}thiophene-2-carboxamide;
  • 5-{(1S)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1-phenylpiperidin-4-yl)-1,3-thiazole-5-carboxamide;
  • 1-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(pyridin-2-yl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • 1-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(phenylacetyl)piperidin-4-yl]phenyl}urea;
  • 5-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 1-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(2,4-difluorobenzoyl)piperdin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(2,5-difluorobenzoyl)piperdin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3,4-difluorobenzoyl)piperdin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3,5-difluorobenzoyl)piperdin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]benzamide;
  • 4-{1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]furan-2-carboxamide;
  • 4-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydro furan-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • 5-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[4-(2-methylpropyl)phenyl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{1-[(2-methylpropyl)sulfonyl]pyrrolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(phenylsulfonyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidine-1-carboxylate;
  • 5-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-{1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2E)-2-methylpent-2-enoyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-{1-[(2,5-dimethylfuran-3-yl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propanoylpyrrolidin-3-yl)thiophene-2-carboxamide;
  • 5-{1-[(1-cyanocyclopropyl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-butanoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyrazin-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(phenylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • 2-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 5-[1-(2-fluorobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 2-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-[2-(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)ethyl]piperazine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • 4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutyl)-1H-pyrazol-5-yl]furan-2-carboxamide;
  • 5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(3-methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-methylbutanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(1-methylpiperidin-4-yl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}acetamide;
  • tert-butyl 4-{4-[(imidazo[1,2-b]pyridazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-b]pyridazin-6-ylmethyl)benzamide;
  • 5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(propan-2-ylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(phenylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 4-{-4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}piperidine-1-carboxylate;
  • N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide;
  • 2-(imidazo[1,2-a]pyridin-6-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}acetamide;
  • N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2-methoxyphenyl)acetyl]amino}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(phenylacetyl)amino]benzamide;
  • 4-(benzoylamino)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 3,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 3,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 2,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 2-fluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-3-methoxybenzamide;
  • 4-{[(2-fluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-2-methoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • 4-(phenylsulfonyl)-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)benzamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tricyclo[3.3.1.1˜3,7]dec-1-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-oxatricyclo[3.3.1.1˜3,7]dec-1-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 4-{[(2,5-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(2,4-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-cyclopropyl-1-(2-methoxy ethyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 4-{[difluoro(phenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(2-methyl-2-phenylpropanoyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate;
  • N-[(3-chloroimidazo[1,2-a]pyrazin-6-yl)methyl]-4-[(cyclopentylacetyl)amino]benzamide;
  • N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • 2-(imidazo[1,2-a]pyridin-7-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}acetamide;
  • 1-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-methyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide;
  • 5-[1-benzyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • N-(2,5-difluorobenzyl)-N′-(imidazo[1,2-a]pyridin-7-ylmethyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(propan-2-yl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbut-2-enoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-fluoro-4-methoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopent-1-en-1-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-ethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxyphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2-acetylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(methoxymethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-phenylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[(2-methylpropyl)sulfonyl]acetyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-phenoxypropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-({[(1R,2S)-2-methylcyclohexyl]oxy}acetyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxyphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylbut-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-methylphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-(4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3-methylbut-2-enoyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopent-1-en-1-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,4-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,5-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-oxo-2,3-dihydro-1H-inden-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-2-methylbut-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(1H-indol-3-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(pyridin-2-yl)cyclopropyl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-dihydro-2H-chromen-6-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(cyclohexyloxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloropyridin-3-yl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2H-chromen-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxycyclohexyl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-1,3-benzoxazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyano cyclopentyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thieno[3,2-b]pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinolin-7-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(5,6,7,8-tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-7-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinoxalin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(2-methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(pyridin-2-yl)prop-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(8-methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methyl-4H-furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-8-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{1-[(4-cyanophenyl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[3-methyl-1-(prop-2-en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)tetrahydro-2H-pyran-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxy-6-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(4-{1-[(2S)-2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(pyridin-2-yl)cyclopropyl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,3-dihydro-1-benzofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxycyclohexyl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-1,3-benzoxazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1-cyanocyclopentyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(cinnolin-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinolin-7-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(5,6,7,8-tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-7-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinoxalin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(2-methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(pyridin-2-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-2,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(8-methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methyl-4H-furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2,3-dihydro-1-benzofuran-5-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-1-ethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-8-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1[(4-cyanophenyl)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[3-methyl-1-(prop-2-en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-{4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-methyl-5-(propan-2-yl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 1-(4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • tert-butyl 4-{3-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(piperidin-1-ylcarbonyl)piperidin-4-yl]benzamide;
  • 1-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(2-fluoro-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2-cyanobenzoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-N,N-dimethylpiperidine-1-carboxamide;
  • 1-{2-fluoro-4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 4-[(cyclopentylacetyl)amino]-N-[(7-fluoroimidazo[1,2-a]pyridin-6-yl)methyl]benzamide;
  • N-[(7-fluoroimidazo[1,2-a]pyridin-6-yl)methyl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-2-(imidazo[1,2-a]pyridin-7-yl)acetamide;
  • 5-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]acetyl}piperidin-4-yl)benzamide;
  • 4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-1-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxy-5-methylpyridin-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[4-(propan-2-yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-5-propyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2,3-dihydro-1-benzofuran-7-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-O-1,3-thiazol-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-(1-{[1-(difluoromethyl)-5-methyl-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazolo[1,5-a]pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-O-1,3-oxazol-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-methylpyridin-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 1-(4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(thieno[3,2-b]furan-5-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxy-5-methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[4-(propan-2-yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-5-propyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(pyrazolo[1,5-a]pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(propan-2-yl)-1,3-oxazol-4-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-7-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxy-5-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • 4-(1-benzoylpiperidin-4-yl)-2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide;
  • 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl]methyl)-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine;
  • 5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin-4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine; and pharmaceutically acceptable salts thereof.


Still another embodiment pertains to compounds of Formula (IB) selected from the group consisting of

  • 4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluoro-4-methoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2-acetylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(methoxymethyl)benzoyl]piperidin-4-yl}benzamide;
  • 4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxy-6-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide; and pharmaceutically acceptable salts thereof.


    Embodiments of Formula (IIB)


In another aspect, the present invention provides compounds of Formula (IIB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IB).


One embodiment pertains to compounds of Formula (IIB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IIB), X is N or CY1. In another embodiment of Formula (IIB), X is N. In another embodiment of Formula (IIB), X is CY1.


In one embodiment of Formula (IIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IIB), X is CY1; and Y1 is Cl. In another embodiment of Formula (IIB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IIB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IIB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, —UN F, Cl, Br and I.


In one embodiment of Formula (IIB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IIB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IIB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (IIB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IIB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IIB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (IIB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IIB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIB)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IIB), which include


4-[(imidazo[1,2-a]pyridin-7-ylcarbamoy)amino]-N-(3-methylbutyl)benzamide; and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IIIB)


In another aspect, the present invention provides compounds of Formula (IIIB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described in Formula (IB) herein.


One embodiment pertains to compounds of Formula (IIIB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IIIB), X is N or CY1. In another embodiment of Formula (IIIB), X is N. In another embodiment of Formula (IIIB), X is CY1.


In one embodiment of Formula (IIIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IIIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IIIB), X is CY1; and Y1 is Cl. In another embodiment of Formula (IIIB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IIIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIIB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IIIB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IIIB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IIIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IIIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IIIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IIIB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IIIB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IIIB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IIIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IIIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (IIIB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IIIB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IIIB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (IIIB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IIIB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIIB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IIIB), which include

  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide;
  • 2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenylethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(morpholin-4-yl)ethyl]benzamide;
  • N-(1-hydroxy-2-methylpropan-2-O-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-benzyl-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-(cyclopentylmethyl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(piperidin-1-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenoxyethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(propan-2-yloxy)ethyl]benzamide;
  • N-(2-hydroxy-2-methylpropyl)-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • N-[2-hydroxy-1-(4-methoxyphenyl)ethyl]-4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[2-(2-oxopyrrolidin-1-yl)ethyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydrofuran-2-ylmethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-propylbenzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(morpholin-4-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-phenylbenzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-methylbutyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-[3-(2-oxopyrrolidin-1-yl)propyl]benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydro-2H-pyran-4-ylmethyl)benzamide;
  • 4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-Netrahydro-2H-pyran-2-ylmethyl)benzamide;
  • N-[(1,1-dioxidotetrahydrothiophen-3-yl)methyl]-4-[(imidazo[1,2-a]pyridin-6-yl carbamoyl)amino]benzamide;


tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;

  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(tetrahydrofuran-3-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(morpholin-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(1-methylpiperidin-4-yl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea;
  • 2-ethoxy-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(morpholin-4-yl)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-2-(2-methoxyethoxy)acetamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3-methoxy-2-methylpropanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}butanamide;
  • 4,4,4-trifluoro-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}butanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}tetrahydro-2H-pyran-4-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-4-methylpentanamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-1-methylpiperidine-4-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide;
  • N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-1,4-dioxane-2-carboxamide;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}piperidine-1-carboxylate;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-imidazo[1,2-a]pyridin-6-ylurea;
  • 1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 4-{[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]amino}-N-(tetrahydro-2H-pyran-2-ylmethyl)benzamide; and pharmaceutically acceptable salts thereof.


    Embodiments of Formula (IVB)


In another aspect, the present invention provides compounds of Formula (IVB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IB).


One embodiment pertains to compounds of Formula (IVB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (IVB), X is N or CY1. In another embodiment of Formula (IVB), X is N. In another embodiment of Formula (IVB), X is CY1.


In one embodiment of Formula (IVB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IVB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IVB), X is CY1; and Y1 is Cl. In another embodiment of Formula (IVB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IVB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IVB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IVB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IVB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IVB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IVB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IVB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IVB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IVB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IVB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IVB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IVB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IVB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (IVB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IVB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IVB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (IVB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IVB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IVB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (IVB), which include

  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro furan-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3-hydroxy-3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide;
  • 3-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)propanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(propan-2-yloxy)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydrofuran-2-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3-phenylpropanamide;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea;
  • tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate;
  • tert-butyl (3R)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate;
  • tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)pyrrolidine-1-carboxylate;
  • N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)biphenyl-2-sulfonamide;
  • 1-{2-fluoro-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro furan-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)urea;
  • tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)azetidine-1-carboxylate;
  • tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)piperidine-1-carboxylate;
  • 1-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydro furan-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydro furan-3-ylcarbonyl]pyrrolidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-yl carbonyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-{4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[5-(piperidin-1-ylcarbonyl)-1,3-thiazol-2-yl]urea;
  • 2-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)-1,3-thiazole-5-carboxamide;
  • 1-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4[(1-benzoylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(propan-2-yloxy)acetyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2R)-tetrahydro furan-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-(4-{[1-(1,4-dioxan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)urea;
  • 1-[4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2R)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(propan-2-yloxy)acetyl]azetidin-3-yl}phenyl)urea;
  • 1-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-phenoxyphenyl)urea;
  • 2-cyclopentyl-N-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • tert-butyl 4-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea;
  • 1-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]urea;
  • 1-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(phenylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea;
  • tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate;
  • 1-(4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3-methylbut-2-enoyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopent-1-en-1-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,4-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,5-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-oxo-2,3-dihydro-1H-inden-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-2-methylbut-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(1H-indol-3-ylacetyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(4-{1-[(2S)-2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(pyridin-2-yl)cyclopropyl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,3-dihydro-1-benzofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxycyclohexyl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-4-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-1,3-benzoxazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1-cyanocyclopentyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(cinnolin-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinolin-7-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(5,6,7,8-tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-7-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinoxalin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(2-methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(pyridin-2-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-2,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(8-methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methyl-4H-furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2,3-dihydro-1-benzofuran-5-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-1-ethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-8-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(4-{1[(4-cyanophenyl)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-{4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[3-methyl-1-(prop-2-en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-{4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(2-fluoro-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(2-cyanobenzoyl)piperidin-4-yl]-2-fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{2-fluoro-4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(thieno[3,2-b]furan-5-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-[4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-{4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxy-5-methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[4-(propan-2-yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-5-propyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(pyrazolo[1,5-a]pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea;
  • 1-{4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(propan-2-yl)-1,3-oxazol-4-yl]carbonyl}piperidin-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-7-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxy-5-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea;
  • 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)phenyl]urea; and pharmaceutically acceptable salts thereof.


    Embodiments of Formula (VB)


In another aspect, the present invention provides compounds of Formula (VB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IB).


One embodiment pertains to compounds of Formula (VB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VB), X is N or CY1. In another embodiment of Formula (VB), X is N. In another embodiment of Formula (VB), X is CY1.


In one embodiment of Formula (VB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VB), X is CY1; and Y1 is Cl. In another embodiment of Formula (VB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (VB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (VB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VB)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VB), which include

  • 4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)benzamide;
  • 2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide;
  • 3-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)propanamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(propan-2-yloxy)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydrofuran-2-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-2-(tetrahydro-2H-pyran-4-yl)acetamide;
  • N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-3-phenylpropanamide;
  • 1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea;
  • 1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea; and pharmaceutically acceptable salts thereof.


    Embodiments of Formula (VIB)


In another aspect, the present invention provides compounds of Formula (VIB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IB).


One embodiment pertains to compounds of Formula (VIB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIB), X is N or CY1. In another embodiment of Formula (VIB), X is N. In another embodiment of Formula (VIB), X is CY1.


In one embodiment of Formula (VIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIB), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (VIB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VIB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VIB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (VIB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VIB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VIB), which include

  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 2-{(4R)-4-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-{(4S)-4-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(1,2-oxazol-3-ylacetyl)[(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(5-methyl-1,2-oxazol-3-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1,2-oxazol-5-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1,2-oxazol-4-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(2R)-tetrahydrofuran-2-ylmethyl](1,3-thiazol-4-ylacetyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,5-dimethyl-1H-pyrazol-3-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1-methyl-1H-pyrazol-4-yl)propanoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[(1-methyl-1H-pyrazol-4-yl)acetyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{[3-(1-methyl-1H-pyrrol-2-yl)propanoyl][(2R)-tetrahydrofuran-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • 2-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-1,3-thiazole-5-carboxamide;
  • tert-butyl {4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[3-(tetrahydrofuran-2-yl)propanoyl]amino}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide;
  • 4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(4-methylpentanoyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 2-{5-[(benzyloxy)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 5-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]thiophene-2-carboxamide;
  • 2-[(2S)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 5-[1-(cyclopropylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]thiophene-2-carboxamide;
  • 2-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(5S)-2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{(5R)-2-oxo-5-[(propan-2-yloxy)methyl]-1,3-oxazolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methoxyacetyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[(4S)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-[1-(cyclohexylmethyl)-5-ethyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methoxy-3,3-dimethylcyclohexyl)methyl]-5-methyl-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl {2-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-(1-ethyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(1,1-dioxidotetrahydrothiophen-3-yl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 2-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-phenylthiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(methylsulfonyl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}pyrrolidine-1-carboxylate;
  • 5-{1-[(2R)-2-hydroxypropyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-3-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydro furan-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3R)-tetrahydro furan-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydro furan-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(propan-2-yloxy)phenyl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(2-methylpropanoyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • 5-[3-(benzoylamino)oxetan-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(tetrahydrofuran-3-ylacetyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(pentanoylamino)oxetan-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3R)-tetrahydro furan-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2R)-tetrahydro furan-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}benzamide;
  • 5-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-3-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • 4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(3-methoxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(3-hydroxy-3-methylbutanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2-(4-benzoylpiperazin-1-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(propan-2-yl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(2-methoxyethyl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-phenyl-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydro furan-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxylate;
  • tert-butyl 4-hydroxy-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 5-{3-hydroxy-1-[(2S)-2-methylbutanoyl]azetidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(3-{[(2S)-2-methylbutanoyl]amino}oxetan-3-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1-[1-(3-methylbutanoyl)piperidin-4-yl]-1H-pyrazole-3-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • tert-butyl (3R)-3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}pyrrolidine-1-carboxylate;
  • 4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3,3-difluorocyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[6-(morpholin-4-yl)pyridin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methyltetrahydro-2H-pyran-2-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylbutanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-{[(2S)-2-methylbutanoyl]amino}cyclobutyl)thiophene-2-carboxamide;
  • 5-[1-(benzoylamino)cyclobutyl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3,3,3-trifluoropropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(1-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}cyclobutyl)tetrahydro-2H-pyran-4-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}azetidine-1-carboxylate;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-phenoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohexylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • 4-(1-butanoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylpent-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyloxetan-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyanocyclopropyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopentylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-oxobutanoyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-propanoylpiperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 5-[4-hydroxy-1-(3-methylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[4-hydroxy-1-(2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)-4-hydroxypiperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylazetidin-3-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • tert-butyl 4-{4-[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-1-ylcarbonyl)benzamide;
  • 4-[1-(ethylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)azetidin-3-yl]benzamide;
  • propan-2-yl-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 2-methylpropyl 4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(2-cyano-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3R)-tetrahydrofuran-3-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(ethylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)azetidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide;
  • 4-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-{(1R)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{(1R)-3-methyl-1-[(tetrahydrofuran-3-ylacetyl)amino]butyl}thiophene-2-carboxamide;
  • 5-{(1S)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1-phenylpiperidin-4-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(pyridin-2-yl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • 5-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]benzamide;
  • 4-{1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]furan-2-carboxamide;
  • 4-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydro furan-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • 5-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[4-(2-methylpropyl)phenyl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{1-[(2-methylpropyl)sulfonyl]pyrrolidin-3-yl}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(phenylsulfonyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidine-1-carboxylate;
  • 5-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-{1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2E)-2-methylpent-2-enoyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-{1-[(2,5-dimethylfuran-3-yl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propanoylpyrrolidin-3-yl)thiophene-2-carboxamide;
  • 5-{1-[(1-cyanocyclopropyl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-butanoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyrazin-2-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]pyrrolidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-carboxamide;
  • 5-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(phenylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide;
  • 2-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 5-[1-(2-fluorobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 2-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-[2-(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)ethyl]piperazine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutyl)-1H-pyrazol-5-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2-methoxyphenyl)acetyl]amino}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(phenylacetyl)amino]benzamide;
  • 4-(benzoylamino)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 3,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 3,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 2,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • 2-fluoro-N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}benzamide;
  • N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-3-methoxybenzamide;
  • 4-{[(2-fluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-2-methoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(phenylsulfonyl)benzamide;
  • 5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tricyclo[3.3.1.1˜3,7˜]dec-1-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-oxatricyclo[3.3.1.1˜3,7˜]dec-1-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 4-{[(2,5-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(2,4-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-cyclopropyl-1-(2-methoxy ethyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-{[difluoro(phenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(2-methyl-2-phenylpropanoyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-methyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide;
  • 5-[1-benzyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(2,5-difluorobenzyl)-N′-(imidazo[1,2-a]pyridin-7-ylmethyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(propan-2-yl)pyrrolidin-1-yl]carbonyl}benzamide;
  • 4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbut-2-enoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-fluoro-4-methoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopent-1-en-1-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-ethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxyphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2-acetylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(methoxymethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-phenylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[(2-methylpropyl)sulfonyl]acetyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-phenoxypropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-({[(1R,2S)-2-methylcyclohexyl]oxy}acetyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxyphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylbut-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-methylphenyl)acetyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(pyridin-2-yl)cyclopropyl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-dihydro-2H-chromen-6-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(cyclohexyloxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloropyridin-3-yl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2H-chromen-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxycyclohexyl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-1,3-benzoxazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyanocyclopentyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thieno[3,2-b]pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinolin-7-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(5,6,7,8-tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-7-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinoxalin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(2-methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(pyridin-2-yl)prop-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(8-methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methyl-4H-furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-8-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{1-[(4-cyanophenyl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[3-methyl-1-(prop-2-en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)tetrahydro-2H-pyran-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxy-6-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-methyl-5-(propan-2-yl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(piperidin-1-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-N,N-dimethylpiperidine-1-carboxamide;
  • 5-{1-[(2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxythiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-pyrazol-3-yl]acetyl}piperidin-4-yl)benzamide;
  • 4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-1-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxy-5-methylpyridin-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[4-(propan-2-yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-5-propyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2,3-dihydro-1-benzo furan-7-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)-1,3-thiazol-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • 4-(1-{[1-(difluoromethyl)-5-methyl-1H-pyrazol-3-yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazolo[1,5-a]pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)-1,3-oxazol-4-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-methylpyridin-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-6-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine;
  • 5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin-4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine; and pharmaceutically acceptable salts thereof.


    Embodiments of Formula (VIIB)


In another aspect, the present invention provides compounds of Formula (VIIB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (IB).


One embodiment pertains to compounds of Formula (VIIB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIIB), X is N or CY1. In another embodiment of Formula (VIIB), X is N. In another embodiment of Formula (VIIB), X is CY1.


In one embodiment of Formula (VIIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIIB), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIIB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIIB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIIB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VIIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIIB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIIB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VIIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (VIIB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VIIB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VIIB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (VIIB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VIIB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIIB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VIIB), which include

  • 4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 2-[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(morpholin-4-ylacetyl)amino]benzamide;
  • 4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(3-phenylpyrrolidin-1-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide;
  • 2-(1,3-dihydro-2H-isoindol-2-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(morpholin-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro furan-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro furan-2-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[3-(tetrahydrofuran-2-yl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide;
  • 4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluorocyclohexyl)carbonyl]-1,2,3,6-tetrahydropyridin-4-yl}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 2-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[2-oxo-4-(tetrahydrofuran-3-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(2-oxo-5-phenyl-1,3-oxazolidin-3-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methyl-1,3-thiazol-5-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methyl-1,3-thiazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(3-methyl-1,2-oxazol-5-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[3-(3-chloro-1,2-oxazol-5-yl)propanoyl](tetrahydro furan-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(3-methoxy-1,2-oxazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 2-{[3-(3,5-dimethyl-1,2-oxazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1-methyl-1H-pyrazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(4-methyl-1,3-thiazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-2-ylmethyl)(1H-tetrazol-5-ylacetyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1,2-oxazol-5-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(1,2-oxazol-3-ylacetyl)(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1,2-oxazol-4-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydrofuran-2-ylmethyl) [3-(1,3-thiazol-2-yl)propanoyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutanoyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydrofuran-3-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-3-ylmethyl)(tetrahydro-2H-pyran-4-ylcarbonyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydrofuran-3-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methoxypropanoyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-3-ylcarbonyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydro-2H-pyran-4-ylcarbonyl)(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(3-methoxypropanoyl)[(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydro furan-3-ylcarbonyl) [(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2R)-tetrahydrofuran-2-ylmethyl](tetrahydro-2H-pyran-4-ylcarbonyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(3-methoxypropanoyl)[(2S)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{(tetrahydro furan-3-ylcarbonyl) [(2S)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2S)-tetrahydro furan-2-ylmethyl](tetrahydro-2H-pyran-4-ylcarbonyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl](tetrahydro-2H-pyran-4-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl][(2R)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-({[2-(propan-2-yloxy)ethyl]carbamoyl}[(2R)-tetrahydrofuran-2-ylmethyl]amino)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(2-methoxyethyl)carbamoyl][(2S)-tetrahydro furan-2-ylmethyl]amino}-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-({[2-(propan-2-yloxy)ethyl]carbamoyl}[(2S)-tetrahydro furan-2-ylmethyl]amino)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-3-ylmethyl)amino]-1,3-thiazole-5-carboxamide;
  • 2-[5-(4-chlorophenyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-[(1-butanoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(3-methoxy-2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropanoyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(cyclohexylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2R)-2-hydroxybutyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[(1-methyl-1H-pyrazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,3-dimethyl-1H-pyrazol-4-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-{[3-(1-methyl-1H-pyrrol-2-yl)propanoyl](tetrahydrofuran-2-ylmethyl)amino}-1,3-thiazole-5-carboxamide;
  • 2-{[(1,5-dimethyl-1H-pyrazol-3-yl)acetyl](tetrahydrofuran-2-ylmethyl)amino}-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(tetrahydrofuran-2-ylmethyl)(1,3-thiazol-4-ylacetyl)amino]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-[(4-cyanobenzyl)(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-6-yl)methyl]-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • 5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(3-methylbutanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • 5-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-{1-[(1-methylpiperidin-4-yl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(propan-2-ylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(phenylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide;
  • 4-(phenylsulfonyl)-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide; and


    pharmaceutically acceptable salts thereof.


    Embodiments of Formula (VIIIB)


In another aspect, the present invention provides compounds of Formula (VIIIB)




embedded image



and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (VIIIB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


In one embodiment of Formula (VIIIB), X is N or CY1. In another embodiment of Formula (VIIIB), X is N. In another embodiment of Formula (VIIIB), X is CY1.


In one embodiment of Formula (VIIIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (VIIIB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (VIIIB), X is CY1; and Y1 is Cl. In another embodiment of Formula (VIIIB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (VIIIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIIB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (VIIIB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (VIIIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (VIIIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (VIIIB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (VIIIB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (VIIIB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (VIIIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (VIIIB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (VIIIB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (VIIIB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (VIIIB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (VIIIB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VIIIB)




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wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the proviso that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent.


Still another embodiment pertains to compounds having Formula (VIIIB), which include


tert-butyl 4-[4-(imidazo[1,2-a]pyridin-7-ylcarbamoyl)phenyl]piperidine-1-carboxylate; and pharmaceutically acceptable salts thereof.


Embodiments of Formula (IXB)


In another aspect, the present invention provides compounds of Formula (IXB)




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and pharmaceutically acceptable salts thereof; wherein X and R3 are as described herein for Formula (I).


One embodiment pertains to compounds of Formula (IXB) or pharmaceutically acceptable salts thereof;


wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent; and


when X is CY1 and Y1 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl.


In one embodiment of Formula (IXB), X is N or CY1. In another embodiment of Formula (IXB), X is N. In another embodiment of Formula (IXB), X is CY1.


In one embodiment of Formula (IXB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, hydroxyalkyl, OH, CN, F, Cl, Br, and I. In another embodiment of Formula (IXB), X is CY1; and Y1 is independently selected from the group consisting of hydrogen, Cl, Br, and I. In another embodiment of Formula (IXB), X is CY1; and Y1 is Cl. In another embodiment of Formula (IXB), X is CY1; and Y1 is hydrogen.


In one embodiment of Formula (IXB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, C(O)H, C(O)OH, C(N)NH2, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, OR4, SR4, S(O)R4, SO2R4, C(O)R4, CO(O)R4, OC(O)R4, OC(O)OR4, NH2, NHR4, N(R4)2, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)NHR4, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR4, C(N)N(R4)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXB), R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IXB), R3 is phenyl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, and C(O)NHR4; and wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I. In another embodiment of Formula (IXB), R3 is 5-6 membered heteroaryl; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I. In another embodiment of Formula (IXB), R3 is thienyl; wherein each R3 thienyl is substituted with one, two, or three substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)NHR4, C(O)NHR4, F, Cl, Br and I.


In one embodiment of Formula (IXB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (IXB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (IXB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (IXB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (IXB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (IXB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (IXB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (IXB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (IXB), R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (IXB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (IXB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (IXB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (IXB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (IXB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IXB)




embedded image



wherein


X is N or CY1;


Y1 is independently selected from the group consisting of hydrogen, F, Cl, Br, and I;


R3 is independently selected from the group consisting of phenyl and 5-6 membered heteroaryl; wherein each R3 phenyl is substituted at the para position with one substituent independently selected from the group consisting of R4, OR4, SO2R4, C(O)R4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NHC(O)OR4, C(O)NHR4, F, Cl, Br and I; wherein each R3 phenyl is optionally additionally substituted with one substituent independently selected from the group consisting of F, Cl, Br and I; wherein each R3 5-6 membered heteroaryl is substituted with one, two, three or four substituents independently selected from the group consisting of R4, C(O)R4, NHR4, NHC(O)R4, NR4C(O)R4, NHC(O)OR4, NR4C(O)OR4, C(O)NHR4, F, Cl, Br and I;


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH;


with the provisos that


when X is CY1 and Y1 is hydrogen; and R3 is thiazolyl; the R3 thiazolyl is substituted with one substituent; and


when X is CY1 and Y1 is hydrogen; and R3 is phenyl; the R3 phenyl is not substituted at the para position with phenyl.


Still another embodiment pertains to compounds having Formula (IXB), which include

  • 2-[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide;
  • 2-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide;
  • 2-cyclopentyl-N-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxoethyl]phenyl}acetamide;
  • tert-butyl 4-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxo ethyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate;
  • tert-butyl 4-[4-(imidazo[1,2-a]pyridin-6-ylcarbamoyl)phenyl]piperidine-1-carboxylate;
  • tert-butyl 4-{4-[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]phenyl}piperidine-1-carboxylate; and pharmaceutically acceptable salts thereof.


    Embodiments of Formula (XB)


In another aspect, the present invention provides compounds of Formula (XB)




embedded image



and pharmaceutically acceptable salts thereof; wherein R4 is as described herein for Formula (IB).


One embodiment pertains to compounds of Formula (XB) or pharmaceutically acceptable salts thereof;


wherein


R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I;


R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I;


R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I; and


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I; and


R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH.


In one embodiment of Formula (XB), R4, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, SR5, S(O)R5, SO2R5, C(O)R5, CO(O)R5, OC(O)R5, OC(O)OR5, NH2, NHR5, N(R5)2, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)NHR5, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR5, C(N)N(R5)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, cycloalkenyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XB), R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, C(O)N(R6)2, OH, and F.


In another embodiment of Formula (XB), R5, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, SR7, S(O)R7, SO2R7, C(O)R7, CO(O)R7, OC(O)R7, OC(O)OR7, NH2, NHR7, N(R7)2, NHC(O)R7, NR7C(O)R7, NHS(O)2R7, NR7S(O)2R7, NHC(O)OR7, NR7C(O)OR7, NHC(O)NH2, NHC(O)NHR7, NHC(O)N(R7)2, NR7C(O)NHR7, NR7C(O)N(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, C(O)NHOH, C(O)NHOR7, C(O)NHSO2R7, C(O)NR7SO2R7, SO2NH2, SO2NHR7, SO2N(R7)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR7, C(N)N(R7)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R5 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, SR8, S(O)R8, SO2R8, C(O)R8, CO(O)R8, OC(O)R8, OC(O)OR8, NH2, NHR8, N(R8)2, NHC(O)R8, NR8C(O)R8, NHS(O)2R8, NR8S(O)2R8, NHC(O)OR8, NR8C(O)OR8, NHC(O)NH2, NHC(O)NHR8, NHC(O)N(R8)2, NR8C(O)NHR8, NR8C(O)N(R8)2, C(O)NH2, C(O)NHR8, C(O)N(R8)2, C(O)NHOH, C(O)NHOR8, C(O)NHSO2R8, C(O)NR8SO2R8, SO2NH2, SO2NHR8, SO2N(R8)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR8, C(N)N(R8)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XB), R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, and OH; wherein each R5 aryl and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I.


In one embodiment of Formula (XB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SR9, S(O)R9, SO2R9, C(O)R9, CO(O)R9, OC(O)R9, OC(O)OR9, NH2, NHR9, N(R9)2, NHC(O)R9, NR9C(O)R9, NHS(O)2R9, NR9S(O)2R9, NHC(O)OR9, NR9C(O)OR9, NHC(O)NH2, NHC(O)NHR9, NHC(O)N(R9)2, NR9C(O)NHR9, NR9C(O)N(R9)2, C(O)NH2, C(O)NHR9, C(O)N(R9)2, C(O)NHOH, C(O)NHOR9, C(O)NHSO2R9, C(O)NR9SO2R9, SO2NH2, SO2NHR9, SO2N(R9)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR9, C(N)N(R9)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, SR10, S(O)R10, SO2R10, C(O)R10, CO(O)R10, OC(O)R10, OC(O)OR10, NH2, NHR10, N(R10)2, NHC(O)R10, NR10C(O)R10, NHS(O)2R10, NR10S(O)2R10, NHC(O)OR10, NR10C(O)OR10, NHC(O)NH2, NHC(O)NHR10, NHC(O)N(R10)2, NR10C(O)NHR10, NR10C(O)N(R10)2, C(O)NH2, C(O)NHR10, C(O)N(R10)2, C(O)NHOH, C(O)NHOR10, C(O)NHSO2R10, C(O)NR10SO2R10, SO2NH2, SO2NHR10, SO2N(R10)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR10, C(N)N(R10)2, CNOH, CNOCH3, OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XB), R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, CN, F, Cl, Br and I.


In one embodiment of Formula (XB), R7, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, N3, NO2, F, Cl, Br and I; wherein each R7 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of OH, CN, N3, NO2, F, Cl, Br and I. In another embodiment of Formula (XB), R7, at each occurrence, is alkyl or heterocyclyl.


In one embodiment of Formula (XB), R8, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, and alkynyl. In another embodiment of Formula (XB), R8, at each occurrence, is independently alkyl.


In one embodiment of Formula (XB), R9, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, OH, CN, NO2, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, OC(O)R11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)H, C(O)OH, COH, CN, NO2, F, Cl, Br and I. In another embodiment of Formula (XB), R9 at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, and alkoxy; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, and F.


In one embodiment of Formula (XB), R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R10 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, F, Cl, Br and I. In another embodiment of Formula (XB), R10, at each occurrence, is independently heterocyclyl, cycloalkyl, alkyl, or alkenyl; wherein each R10 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F.


In one embodiment of Formula (XB), R11, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkyl, alkenyl, and alkynyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH. In another embodiment of Formula (XB), R11, at each occurrence, is independently alkyl. In another embodiment of Formula (XB), R11, at each occurrence, is independently cycloalkyl.


One embodiment pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (XB)




embedded image



wherein


R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, and 3-12 membered heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R5, OR5, C(O)R5, NHC(O)R5, OH, F, Cl, Br and I; wherein each R4 aryl, cycloalkyl, and 3-12 membered heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R6, OR6, SO2R6, C(O)R6, CO(O)R6, C(O)C(O)R6, NHC(O)R6, NHC(O)NHR6, C(O)N(R6)2, OH, F, Cl, Br and I;


R5, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R5 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R7, OR7, OH, F, Cl, Br and I; wherein each R5 aryl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R8, OR8, CN, F, Cl, Br and I;


R6, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R6 alkyl and alkenyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R9, OR9, SO2R9, NH2, N(R9)2, OH, F, Cl, Br and I; wherein each R6 aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R10, OR10, C(O)R10, CN, F, and Cl;


R7, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;


R8, at each occurrence, is independently alkyl;


R9, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of aryl, alkoxy, F, Cl, Br and I; wherein each R9 aryl, cycloalkyl, and heterocyclyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of R11, OR11, C(O)R11, CO(O)R11, CN, F, Cl, Br and I;


R10, at each occurrence, is independently selected from the group consisting of aryl, heterocyclyl, cycloalkyl, alkyl, and alkenyl; wherein each R19 alkyl is optionally substituted with one, two, three or four substituents independently selected from the group consisting of alkoxy, and F; and


R11, at each occurrence, is independently cycloalkyl or alkyl; wherein each R11 alkyl is optionally substituted with NH(CH3), heterocyclyl, SCH2CH(NH2)C(O)OH, OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2NH2, or NHC(O)CH2CH(NH2)C(O)OH.


Still another embodiment pertains to compounds having Formula (XB), which include

  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-phenylthiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(methylsulfonyl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}pyrrolidine-1-carboxylate;
  • 5-{1-[(2R)-2-hydroxypropyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-3-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide;
  • 5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(propan-2-yloxy)phenyl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(2-methylpropanoyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • 5-[3-(benzoylamino)oxetan-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(tetrahydrofuran-3-ylacetyl)amino]oxetan-3-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(pentanoylamino)oxetan-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3R)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}benzamide;
  • 5-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-3-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • 4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(3-methoxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{[(3S)-1-(3-hydroxy-3-methylbutanoyl)pyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 2-(4-benzoylpiperazin-1-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(propan-2-yl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(2-methoxyethyl)piperazin-1-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-phenyl-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide;
  • tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-yloxy)acetyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(1,4-dioxan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxylate;
  • tert-butyl 4-hydroxy-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperdine-1-carboxylate;
  • 5-{3-hydroxy-1-[(2S)-2-methylbutanoyl]azetidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[3-hydroxy-1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(3-{[(2S)-2-methylbutanoyl]amino}oxetan-3-yl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1-[1-(3-methylbutanoyl)piperidin-4-yl]-1H-pyrazole-3-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-[(1-acetylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylpiperidin-4-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(propan-2-yloxy)acetyl]piperidin-4-yl}oxy)benzamide;
  • 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}benzamide;
  • 4-{[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}benzamide;
  • tert-butyl (3R)-3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}pyrrolidine-1-carboxylate;
  • 4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(3,3-difluorocyclobutyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(4,4-difluoro cyclohexyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[6-(morpholin-4-yl)pyridin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methyltetrahydro-2H-pyran-2-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylbutanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-{[(2S)-2-methylbutanoyl]amino}cyclobutyl)thiophene-2-carboxamide;
  • 5-[1-(benzoylamino)cyclobutyl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3,3,3-trifluoropropanoyl)amino]cyclobutyl}thiophene-2-carboxamide;
  • N-(1-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}cyclobutyl)tetrahydro-2H-pyran-4-carboxamide;
  • tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}azetidine-1-carboxylate;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-3-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]furan-2-carboxamide;
  • 5-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide;
  • 5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide;
  • 4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-phenoxybenzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide;
  • 4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide;
  • 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclohexylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide;
  • 4-(1-butanoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylpent-2-enoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyloxetan-3-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-{1-[(1-cyanocyclopropyl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopentylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-oxobutanoyl)piperidin-4-yl]benzamide;
  • 4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • 4-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)piperidin-4-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-propanoylpiperidin-4-yl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)piperidin-4-yl]benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide;
  • 5-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 2-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide;
  • 4-[(cyclopentylacetyl)amino]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopropylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-(1-benzoylazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 5-[4-hydroxy-1-(3-methylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[4-hydroxy-1-(2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-[1(3,3-dimethylbutanoyl)-4-hydroxypiperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 5-(1-benzoyl-4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)benzamide;
  • 4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[(1-benzoylazetidin-3-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • tert-butyl 4-{4-[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-1-ylcarbonyl)benzamide;
  • 4-[1-(ethylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)azetidin-3-yl]benzamide;
  • propan-2-yl-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • 2-methylpropyl 4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]piperidin-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide;
  • N-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • 5-[1-(2-cyano-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
  • 4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3R)-tetrahydro furan-3-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 4-[1-(ethylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(cyclopropylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)pyrrolidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclopentylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylpentanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclopentylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(2-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylbenzoyl)azetidin-3-yl]benzamide;
  • 4-[1-(4-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-chlorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(4-fluorobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbutanoyl)azetidin-3-yl]benzamide;
  • 4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3-cyanobenzoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-methoxybenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(cyclohexylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(cyclohexylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • 4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}benzamide;
  • 4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbenzoyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]azetidin-3-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)pyrrolidin-3-yl]benzamide;
  • 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide;
  • 4-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 5-{(1R)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{(1R)-3-methyl-1-[(tetrahydrofuran-3-ylacetyl)amino]butyl}thiophene-2-carboxamide;
  • 5-{(1S)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1-phenylpiperidin-4-yl)-1,3-thiazole-5-carboxamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(pyridin-2-yl)piperidin-4-yl]-1,3-thiazole-5-carboxamide;
  • 5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;
  • 4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • 4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)piperidin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide;
  • N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide; and pharmaceutically acceptable salts thereof.


    Pharmaceutical Compositions, Combination Therapies, Methods of Treatment, and Administration


Another embodiment comprises pharmaceutical compositions comprising a compound having Formula (I) and an excipient.


Still another embodiment comprises methods of treating cancer in a mammal comprising administering thereto a therapeutically acceptable amount of a compound having Formula (I).


Still another embodiment pertains to compositions for treating diseases during which NAMPT is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I).


Still another embodiment pertains to methods of treating disease in a patient during which NAMPT is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).


Still another embodiment pertains to compositions for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I).


Still another embodiment pertains to methods of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).


Still another embodiment pertains to compositions for treating diseases during which NAMPT is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.


Still another embodiment pertains to methods of treating disease in a patient during which NAMPT is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.


Still another embodiment pertains to compositions for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.


Still another embodiment pertains to methods of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said methods comprising administering to the patient a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.


Metabolites of compounds having Formula (I), produced by in vitro or in vivo metabolic processes, may also have utility for treating diseases associated with NAMPT.


Certain precursor compounds which may be metabolized in vitro or in vivo to form compounds having Formula (I) may also have utility for treating diseases associated with NAMPT.


Compounds having Formula (I) may exist as acid addition salts, basic addition salts or zwitterions. Salts of the compounds are prepared during isolation or following purification of the compounds. Acid addition salts of the compounds are those derived from the reaction of the compounds with an acid. For example, the acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, formate, fumarate, glycerophosphate, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, trifluoroacetic, para-toluenesulfonate, and undecanoate salts of the compounds are contemplated as being embraced by this invention. Basic addition salts of the compounds are those derived from the reaction of the compounds with the hydroxide, carbonate or bicarbonate of cations such as lithium, sodium, potassium, calcium, and magnesium.


The compounds having Formula (I) may be administered, for example, bucally, ophthalmically, orally, osmotically, parenterally (intramuscularly, intraperitoneally intrasternally, intravenously, subcutaneously), rectally, topically, transdermally or vaginally.


Therapeutically effective amounts of compounds having Formula (I) depend on the recipient of the treatment, the disorder being treated and the severity thereof, the composition containing the compound, the time of administration, the route of administration, the duration of treatment, the compound potency, its rate of clearance and whether or not another drug is co-administered. The amount of a compound of this invention having Formula (I) used to make a composition to be administered daily to a patient in a single dose or in divided doses is from about 0.03 to about 200 mg/kg body weight. Single dose compositions contain these amounts or a combination of submultiples thereof.


Compounds having Formula (I) may be administered with or without an excipient. Excipients include, for example, encapsulating materials or additives such as absorption accelerators, antioxidants, binders, buffers, coating agents, coloring agents, diluents, disintegrating agents, emulsifiers, extenders, fillers, flavoring agents, humectants, lubricants, perfumes, preservatives, propellants, releasing agents, sterilizing agents, sweeteners, solubilizers, wetting agents and mixtures thereof.


Excipients for preparation of compositions comprising a compound having Formula (I) to be administered orally in solid dosage form include, for example, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate, 1,3-butylene glycol, carbomers, castor oil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil, cottonseed oil, cross-povidone, diglycerides, ethanol, ethyl cellulose, ethyl laureate, ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol, groundnut oil, hydroxypropylmethyl cellulose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, peanut oil, potassium phosphate salts, potato starch, povidone, propylene glycol, Ringer's solution, safflower oil, sesame oil, sodium carboxymethyl cellulose, sodium phosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil, stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth, tetrahydrofurfuryl alcohol, triglycerides, water, and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered ophthalmically or orally in liquid dosage forms include, for example, 1,3-butylene glycol, castor oil, corn oil, cottonseed oil, ethanol, fatty acid esters of sorbitan, germ oil, groundnut oil, glycerol, isopropanol, olive oil, polyethylene glycols, propylene glycol, sesame oil, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered osmotically include, for example, chlorofluorohydrocarbons, ethanol, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered parenterally include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, germ oil, groundnut oil, liposomes, oleic acid, olive oil, peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil, U.S.P. or isotonic sodium chloride solution, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered rectally or vaginally include, for example, cocoa butter, polyethylene glycol, wax and mixtures thereof.


Compounds having Formula (I) are expected to be useful when used with alkylating agents, angiogenesis inhibitors, antibodies, antimetabolites, antimitotics, antiproliferatives, antivirals, aurora kinase inhibitors, apoptosis promoters (for example, Bcl-xL, Bcl-w and Bfl-1) inhibitors, activators of death receptor pathway, Bcr-Abl kinase inhibitors, BiTE (Bi-Specific T cell Engager) antibodies, antibody drug conjugates, biologic response modifiers, cyclin-dependent kinase inhibitors, cell cycle inhibitors, cyclooxygenase-2 inhibitors, DVDs, leukemia viral oncogene homolog (ErbB2) receptor inhibitors, growth factor inhibitors, heat shock protein (HSP)-90 inhibitors, histone deacetylase (HDAC) inhibitors, hormonal therapies, immunologicals, inhibitors of inhibitors of apoptosis proteins (IAPs), intercalating antibiotics, kinase inhibitors, kinesin inhibitors, Jak2 inhibitors, mammalian target of rapamycin inhibitors, microRNA's, mitogen-activated extracellular signal-regulated kinase inhibitors, multivalent binding proteins, non-steroidal anti-inflammatory drugs (NSAIDs), poly ADP (adenosine diphosphate)-ribose polymerase (PARP) inhibitors, platinum chemotherapeutics, polo-like kinase (Plk) inhibitors, phosphoinositide-3 kinase (PI3K) inhibitors, proteosome inhibitors, purine analogs, pyrimidine analogs, receptor tyrosine kinase inhibitors, retinoids/deltoids plant alkaloids, small inhibitory ribonucleic acids (siRNAs), topoisomerase inhibitors, ubiquitin ligase inhibitors, and the like, and in combination with one or more of these agents.


BiTE antibodies are bi-specific antibodies that direct T-cells to attack cancer cells by simultaneously binding the two cells. The T-cell then attacks the target cancer cell. Examples of BiTE antibodies include adecatumumab (Micromet MT201), blinatumomab (Micromet MT103) and the like. Without being limited by theory, one of the mechanisms by which T-cells elicit apoptosis of the target cancer cell is by exocytosis of cytolytic granule components, which include perforin and granzyme B.


SiRNAs are molecules having endogenous RNA bases or chemically modified nucleotides. The modifications do not abolish cellular activity, but rather impart increased stability and/or increased cellular potency. Examples of chemical modifications include phosphorothioate groups, 2′-deoxynucleotide, 2′-OCH3-containing ribonucleotides, 2′-F-ribonucleotides, 2′-methoxyethyl ribonucleotides, combinations thereof and the like. The siRNA can have varying lengths (e.g., 10-200 bps) and structures (e.g., hairpins, single/double strands, bulges, nicks/gaps, mismatches) and are processed in cells to provide active gene silencing. A double-stranded siRNA (dsRNA) can have the same number of nucleotides on each strand (blunt ends) or asymmetric ends (overhangs). The overhang of 1-2 nucleotides can be present on the sense and/or the antisense strand, as well as present on the 5′- and/or the 3′-ends of a given strand.


Multivalent binding proteins are binding proteins comprising two or more antigen binding sites. Multivalent binding proteins are engineered to have the three or more antigen binding sites and are generally not naturally occurring antibodies. The term “multispecific binding protein” means a binding protein capable of binding two or more related or unrelated targets. Dual variable domain (DVD) binding proteins are tetravalent or multivalent binding proteins binding proteins comprising two or more antigen binding sites. Such DVDs may be monospecific (i.e., capable of binding one antigen) or multispecific (i.e., capable of binding two or more antigens). DVD binding proteins comprising two heavy chain DVD polypeptides and two light chain DVD polypeptides are referred to as DVD Ig's. Each half of a DVD Ig comprises a heavy chain DVD polypeptide, a light chain DVD polypeptide, and two antigen binding sites. Each binding site comprises a heavy chain variable domain and a light chain variable domain with a total of 6 CDRs involved in antigen binding per antigen binding site.


Alkylating agents include altretamine, AMD-473, AP-5280, apaziquone, bendamustine, brostallicin, busulfan, carboquone, carmustine (BCNU), chlorambucil, CLORETAZINE® (laromustine, VNP 40101M), cyclophosphamide, decarbazine, estramustine, fotemustine, glufosfamide, ifosfamide, KW-2170, lomustine (CCNU), mafosfamide, melphalan, mitobronitol, mitolactol, nimustine, nitrogen mustard N-oxide, ranimustine, temozolomide, thiotepa, TREANDA® (bendamustine), treosulfan, trofosfamide and the like.


Angiogenesis inhibitors include endothelial-specific receptor tyrosine kinase (Tie-2) inhibitors, epidermal growth factor receptor (EGFR) inhibitors, insulin growth factor-2 receptor (IGFR-2) inhibitors, matrix metalloproteinase-2 (MMP-2) inhibitors, matrix metalloproteinase-9 (MMP-9) inhibitors, platelet-derived growth factor receptor (PDGFR) inhibitors, thrombospondin analogs, vascular endothelial growth factor receptor tyrosine kinase (VEGFR) inhibitors and the like.


Antimetabolites include ALIMTA® (pemetrexed disodium, LY231514, MTA), 5-azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribine), clofarabine, cytarabine, cytarabine ocfosfate, cytosine arabinoside, decitabine, deferoxamine, doxifluridine, eflornithine, EICAR (5-ethynyl-1-(3-D-ribofuranosylimidazole-4-carboxamide), enocitabine, ethnylcytidine, fludarabine, 5-fluorouracil alone or in combination with leucovorin, GEMZAR® (gemcitabine), hydroxyurea, ALKERAN® (melphalan), mercaptopurine, 6-mercaptopurine riboside, methotrexate, mycophenolic acid, nelarabine, nolatrexed, ocfosfate, pelitrexol, pentostatin, raltitrexed, Ribavirin, triapine, trimetrexate, S-1, tiazofurin, tegafur, TS-1, vidarabine, UFT and the like.


Antivirals include ritonavir, hydroxychloroquine and the like.


Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680, Aurora A-specific kinase inhibitors, Aurora B-specific kinase inhibitors and pan-Aurora kinase inhibitors and the like.


Bcl-2 protein inhibitors include AT-101 ((−)gossypol), GENASENSE® (G3139 or oblimersen (Bcl-2-targeting antisense oligonucleotide)), IPI-194, IPI-565, N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide) (ABT-737), N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide (ABT-263), GX-070 (obatoclax) and the like.


Bcr-Abl kinase inhibitors include DASATINIB® (BMS-354825), GLEEVEC® (imatinib) and the like.


CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584, flavopyridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib (CYC-202, R-roscovitine), ZK-304709 and the like.


COX-2 inhibitors include ABT-963, ARCOXIA® (etoricoxib), BEXTRA® (valdecoxib), BMS347070, CELEBREX® (celecoxib), COX-189 (lumiracoxib), CT-3, DERAMAXX® (deracoxib), JTE-522, 4-methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl-1H-pyrrole), MK-663 (etoricoxib), NS-398, parecoxib, RS-57067, SC-58125, SD-8381, SVT-2016, S-2474, T-614, VIOXX® (rofecoxib) and the like.


EGFR inhibitors include ABX-EGF, anti-EGFR immunoliposomes, EGF-vaccine, EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibodies, IRESSA® (gefitinib), TARCEVA® (erlotinib or OSI-774), TP-38, EGFR fusion protein, TYKERB® (lapatinib) and the like.


ErbB2 receptor inhibitors include CP-724-714, CI-1033 (canertinib), HERCEPTIN® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4, petuzumab), TAK-165, GW-572016 (ionafarnib), GW-282974, EKB-569, PI-166, dHER2 (HER2 vaccine), APC-8024 (HER-2 vaccine), anti-HER/2neu bispecific antibody, B7.her2IgG3, AS HER2 trifunctional bispecfic antibodies, mAB AR-209, mAB 2B-1 and the like.


Histone deacetylase inhibitors include depsipeptide, LAQ-824, MS-275, trapoxin, suberoylanilide hydroxamic acid (SAHA), TSA, valproic acid and the like.


HSP-90 inhibitors include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010, CNF-2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB® (human recombinant antibody to HSP-90), NCS-683664, PU24FCl, PU-3, radicicol, SNX-2112, STA-9090 VER49009 and the like.


Inhibitors of inhibitors of apoptosis proteins include HGS1029, GDC-0145, GDC-0152, LCL-161, LBW-242 and the like.


Antibody drug conjugates include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE, anti-CD22-MCC-DM1, CR-011-vcMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35, SGN-75 and the like


Activators of death receptor pathway include TRAIL, antibodies or other agents that target TRAIL or death receptors (e.g., DR4 and DR5) such as Apomab, conatumumab, ETR2-ST01, GDC0145 (lexatumumab), HGS-1029, LBY-135, PRO-1762 and trastuzumab.


Kinesin inhibitors include Eg5 inhibitors such as AZD4877, ARRY-520; CENPE inhibitors such as GSK923295A and the like.


JAK-2 inhibitors include CEP-701 (lesaurtinib), XL019 and INCB018424 and the like.


MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 and the like.


mTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001, rapamycin, temsirolimus, ATP-competitive TORC1/TORC2 inhibitors, including PI-103, PP242, PP30, Torin 1 and the like.


Non-steroidal anti-inflammatory drugs include AMIGESIC® (salsalate), DOLOBID® (diflunisal), MOTRIN® (ibuprofen), ORUDIS® (ketoprofen), RELAFEN® (nabumetone), FELDENE® (piroxicam), ibuprofen cream, ALEVE® (naproxen) and NAPROSYN® (naproxen), VOLTAREN® (diclofenac), INDOCIN® (indomethacin), CLINORIL® (sulindac), TOLECTIN® (tolmetin), LODINE® (etodolac), TORADOL® (ketorolac), DAYPRO® (oxaprozin) and the like.


PDGFR inhibitors include C-451, CP-673, CP-868596 and the like.


Platinum chemotherapeutics include cisplatin, ELOXATIN® (oxaliplatin) eptaplatin, lobaplatin, nedaplatin, PARAPLATIN® (carboplatin), satraplatin, picoplatin and the like.


Polo-like kinase inhibitors include BI-2536 and the like.


Phosphoinositide-3 kinase (PI3K) inhibitors include wortmannin, LY294002, XL-147, CAL-120, ONC-21, AEZS-127, ETP-45658, PX-866, GDC-0941, BGT226, BEZ235, XL765 and the like.


Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and the like.


VEGFR inhibitors include AVASTIN® (bevacizumab), ABT-869, AEE-788, ANGIOZYME™ (a ribozyme that inhibits angiogenesis (Ribozyme Pharmaceuticals (Boulder, Colo.) and Chiron, (Emeryville, Calif.)), axitinib (AG-13736), AZD-2171, CP-547, 632, IM-862, MACUGEN (pegaptamib), NEXAVAR® (sorafenib, BAY43-9006), pazopanib (GW-786034), vatalanib (PTK-787, ZK-222584), SUTENT® (sunitinib, SU-11248), VEGF trap, ZACTIMA™ (vandetanib, ZD-6474) and the like.


Antibiotics include intercalating antibiotics aclarubicin, actinomycin D, amrubicin, annamycin, adriamycin, BLENOXANE® (bleomycin), daunorubicin, CAELYX® or MYOCET® (liposomal doxorubicin), elsamitrucin, epirbucin, glarbuicin, ZAVEDOS® (idarubicin), mitomycin C, nemorubicin, neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, stimalamer, streptozocin, VALSTAR® (valrubicin), zinostatin and the like.


Topoisomerase inhibitors include aclarubicin, 9-aminocamptothecin, amonafide, amsacrine, becatecarin, belotecan, BN-80915, CAMPTOSAR® (irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxine), diflomotecan, edotecarin, ELLENCE® or PHARMORUBICIN® (epirubicin), etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan, mitoxantrone, orathecin, pirarbucin, pixantrone, rubitecan, sobuzoxane, SN-38, tafluposide, topotecan and the like.


Antibodies include AVASTIN® (bevacizumab), CD40-specific antibodies, chTNT-1/B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab), IGF1R-specific antibodies, lintuzumab, PANOREX® (edrecolomab), RENCAREX® (WX G250), RITUXAN® (rituximab), ticilimumab, trastuzimab, CD20 antibodies types I and II and the like.


Hormonal therapies include ARIMIDEX (anastrozole), AROMASIN (exemestane), arzoxifene, CASODEX® (bicalutamide), CETROTIDE® (cetrorelix), degarelix, deslorelin, DESOPAN® (trilostane), dexamethasone, DROGENIL® (flutamide), EVISTA® (raloxifene), AFEMA™ (fadrozole), FARESTON® (toremifene), FASLODEX® (fulvestrant), FEMARA® (letrozole), formestane, glucocorticoids, HECTOROL® (doxercalciferol), RENAGEL® (sevelamer carbonate), lasofoxifene, leuprolide acetate, MEGACE® (megesterol), MIFEPREX® (mifepristone), NILANDRON™ (nilutamide), NOLVADEX® (tamoxifen citrate), PLENAXIS™ (abarelix), prednisone, PROPECIA® (finasteride), rilostane, SUPREFACT® (buserelin), TRELSTAR® (luteinizing hormone releasing hormone (LHRH)), VANTAS® (Histrelin implant), VETORYL® (trilostane or modrastane), ZOLADEX® (fosrelin, goserelin) and the like.


Deltoids and retinoids include seocalcitol (EB1089, CB1093), lexacalcitrol (KH1060), fenretinide, PANRETIN® (aliretinoin), ATRAGEN® (liposomal tretinoin), TARGRETIN® (bexarotene), LGD-1550 and the like.


PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436, AZD-2281, AG-014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.


Plant alkaloids include, but are not limited to, vincristine, vinblastine, vindesine, vinorelbine and the like.


Proteasome inhibitors include VELCADE® (bortezomib), MG132, NPI-0052, PR-171 and the like.


Examples of immunologicals include interferons and other immune-enhancing agents. Interferons include interferon alpha, interferon alpha-2a, interferon alpha-2b, interferon beta, interferon gamma-1a, ACTIMMUNE® (interferon gamma-1b) or interferon gamma-n1, combinations thereof and the like. Other agents include ALFAFERONE®, (IFN-α), BAM-002 (oxidized glutathione), BEROMUN® (tasonermin), BEXXAR® (tositumomab), CAMPATH® (alemtuzumab), CTLA4 (cytotoxic lymphocyte antigen 4), decarbazine, denileukin, epratuzumab, GRANOCYTE® (lenograstim), lentinan, leukocyte alpha interferon, imiquimod, MDX-010 (anti-CTLA-4), melanoma vaccine, mitumomab, molgramostim, MYLOTARG™ (gemtuzumab ozogamicin), NEUPOGEN® (filgrastim), OncoVAC-CL, OVAREX® (oregovomab), pemtumomab (Y-muHMFG1), PROVENGE® (sipuleucel-T), sargaramostim, sizofilan, teceleukin, THERACYS® (Bacillus Calmette-Guerin), ubenimex, VIRULIZIN® (immunotherapeutic, Lorus Pharmaceuticals), Z-100 (Specific Substance of Maruyama (SSM)), WF-10 (Tetrachlorodecaoxide (TCDO)), PROLEUKIN® (aldesleukin), ZADAXIN® (thymalfasin), ZENAPAX® (daclizumab), ZEVALIN® (90Y-Ibritumomab tiuxetan) and the like.


Biological response modifiers are agents that modify defense mechanisms of living organisms or biological responses, such as survival, growth or differentiation of tissue cells to direct them to have anti-tumor activity and include krestin, lentinan, sizofuran, picibanil PF-3512676 (CpG-8954), ubenimex and the like.


Pyrimidine analogs include cytarabine (ara C or Arabinoside C), cytosine arabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU (5-fluorouracil), floxuridine, GEMZAR® (gemcitabine), TOMUDEX® (ratitrexed), TROXATYL™ (triacetyluridine troxacitabine) and the like.


Purine analogs include LANVIS® (thioguanine) and PURI-NETHOL® (mercaptopurine).


Antimitotic agents include batabulin, epothilone D (KOS-862), N-(2-((4-hydroxyphenyl)amino)pyridin-3-yl)-4-methoxybenzenesulfonamide, ixabepilone (BMS 247550), paclitaxel, TAXOTERE® (docetaxel), PNU100940 (109881), patupilone, XRP-9881 (larotaxel), vinflunine, ZK-EPO (synthetic epothilone) and the like.


Ubiquitin ligase inhibitors include MDM2 inhibitors, such as nutlins, NEDD8 inhibitors such as MLN4924 and the like.


Compounds of this invention can also be used as radiosensitizers that enhance the efficacy of radiotherapy. Examples of radiotherapy include external beam radiotherapy, teletherapy, brachytherapy and sealed, unsealed source radiotherapy and the like.


Additionally, compounds having Formula (I) may be combined with other chemotherapeutic agents such as ABRAXANE™ (ABI-007), ABT-100 (farnesyl transferase inhibitor), ADVEXIN® (Ad5CMV-p53 vaccine), ALTOCOR® or MEVACOR® (lovastatin), AMPLIGEN® (poly I:poly C12U, a synthetic RNA), APTOSYN® (exisulind), AREDIA® (pamidronic acid), arglabin, L-asparaginase, atamestane (1-methyl-3,17-dione-androsta-1,4-diene), AVAGE® (tazarotene), AVE-8062 (combreastatin derivative) BEC2 (mitumomab), cachectin or cachexin (tumor necrosis factor), canvaxin (vaccine), CEAVAC® (cancer vaccine), CELEUK® (celmoleukin), CEPLENE® (histamine dihydrochloride), CERVARIX® (human papillomavirus vaccine), CHOP® (C: CYTOXAN® (cyclophosphamide); H: ADRIAMYCIN® (hydroxydoxorubicin); O: Vincristine (ONCOVIN®); P: prednisone), CYPAT™ (cyproterone acetate), combrestatin A4P, DAB(389)EGF (catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor) or TransMID-107R™ (diphtheria toxins), dacarbazine, dactinomycin, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), eniluracil, EVIZON™ (squalamine lactate), DIMERICINE® (T4N5 liposome lotion), discodermolide, DX-8951f (exatecan mesylate), enzastaurin, EPO906 (epithilone B), GARDASIL® (quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine), GASTRIMMUNE®, GENASENSE®, GMK (ganglioside conjugate vaccine), GVAX® (prostate cancer vaccine), halofuginone, histerelin, hydroxycarbamide, ibandronic acid, IGN-101, IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), IL-13-pseudomonas exotoxin, interferon-α, interferon-γ, JUNOVAN™ or MEPACT™ (mifamurtide), lonafarnib, 5,10-methylenetetrahydrofolate, miltefosine (hexadecylphosphocholine), NEOVASTAT® (AE-941), NEUTREXIN® (trimetrexate glucuronate), NIPENT® (pentostatin), ONCONASE® (a ribonuclease enzyme), ONCOPHAGE® (melanoma vaccine treatment), ONCOVAX® (IL-2 Vaccine), ORATHECIN™ (rubitecan), OSIDEM® (antibody-based cell drug), OVAREX® MAb (murine monoclonal antibody), paclitaxel, PANDIMEX™ (aglycone saponins from ginseng comprising 20(S)protopanaxadiol (aPPD) and 20(S)protopanaxatriol (aPPT)), panitumumab, PANVAC®-VF (investigational cancer vaccine), pegaspargase, PEG Interferon A, phenoxodiol, procarbazine, rebimastat, REMOVAB® (catumaxomab), REVLIMID® (lenalidomide), RSR13 (efaproxiral), SOMATULINE® LA (lanreotide), SORIATANE® (acitretin), staurosporine (Streptomyces staurospores), talabostat (PT100), TARGRETIN® (bexarotene), TAXOPREXIN® (DHA-paclitaxel), TELCYTA® (canfosfamide, TLK286), temilifene, TEMODAR® (temozolomide), tesmilifene, thalidomide, THERATOPE® (STn-KLH), thymitaq (2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)quinazoline dihydrochloride), TNFERADE™ (adenovector: DNA carrier containing the gene for tumor necrosis factor-α), TRACLEER® or ZAVESCA® (bosentan), tretinoin (Retin-A), tetrandrine, TRISENOX® (arsenic trioxide), VIRULIZIN®, ukrain (derivative of alkaloids from the greater celandine plant), vitaxin (anti-alphavbeta3 antibody), XCYTRIN® (motexafin gadolinium), XINLAY™ (atrasentan), XYOTAX™ (paclitaxel poliglumex), YONDELIS® (trabectedin), ZD-6126, ZINECARD® (dexrazoxane), ZOMETA® (zolendronic acid), zorubicin and the like.


Data


Determination of the utility of compounds having Formula (I) as binders to and inhibitors of NAMPT was performed using Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) binding assays.


Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay of NAMPT

Test compounds were serially diluted (typically 11 half log dilutions) in neat DMSO to 50× final concentrations prior to dilution with assay buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) to 3× and 6% DMSO. Six μL were transferred to 384-well low-volume plates (Owens Corning #3673). To this, 12 pt of a 1.5× solution containing enzyme, probe and antibody were added. Final concentrations in the 18 μL, reactions were 1× assay buffer, 2% DMSO, 6.8 nM NAMPT (human, recombinant, C-terminally His-tagged), 200 nM probe (a potent nicotinamide-competitive inhibitor conjugated to Oregon Green 488) and 1 nM Tb-anti-His antibody (Invitrogen # PV5895). Reactions were equilibrated at room temperature for 3 hours prior to reading on an Envision multi-label plate reader (Perkin Elmer; Ex=337 nm, Em=520 and 495 nm). Time-resolved FRET ratios (Em520/Em495) were normalized to controls, plotted as a function of compound concentration and fit with the four-parameter logistic equation to determine IC50s.


Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay of NAMPT with PRPP

Compound handling and data processing were identical to the assay in the absence of substrates (above). Final concentrations were 1× assay buffer, 2% DMSO, 2 nM NAMPT, 2 nM probe, 1 nM Tb-anti-His antibody (Invitrogen # PV5895), 200 μM PRPP and 2.5 mM ATP. Reactions were equilibrated for 16 hours prior to measurement to allow for potential enzymatic modification of test compounds.


Table 1 shows the utility of compounds having Formula I to functionally inhibit NAMPT.











TABLE 1







TR-FRET



TR-FRET
Binding-IC50



Binding-IC50
(with PRPP)


Example
(μM)
(μM)

















1
0.0921
0.00072


2
0.854
0.0398


3
0.0316
0.000282


4
0.413
0.000516


5
2.5
0.000684


6
2.91
0.000964


7
0.183
0.000516


8
0.114
0.000702


9
1.72
0.000459


10
0.197
0.000457


11
7.6
0.000271


12
0.486
0.000292


13
0.653
0.000663


14
0.741
0.00122


15
1.76
0.000841


16
0.409
0.000396


17
2.96
0.000401


18
2.73
0.000418


19
2.68
0.000921


20
0.404
0.000169


21
0.433
0.000887


22
0.399
0.000277


23
0.281
0.000409


24
0.167
0.000363


25
0.508
0.000714


26
0.211
0.0011


27
0.756
0.000658


28
0.152
0.00019


29
0.168
0.000236


30
1.18
0.000785


31
0.739
0.000311


32
0.906
0.000169


33
0.369
0.000553


34
0.208
0.000377


35
0.387
0.000801


36
0.356
0.000444


37
0.129
0.000309


38
0.243
0.000266


39
0.814
0.00026


40
0.0409
0.000217


41
0.294
0.00115


42
0.697
0.000381


43
4.35
0.000169


44
0.396
0.000496


45
0.879
0.00119


46
0.773
0.000318


47
0.0575
0.00062


48
>10
0.000169


49
0.442
0.000317


50
1.64
0.000817


51
0.264
0.000524


52
0.0186
0.00579


53
4.45
0.0144


54
0.363
0.00255


55
0.364
0.00137


56
0.158
0.00107


57
0.0058



58
0.523
0.00143


59
0.222
0.000695


60
0.00861
0.00149


61
0.0782
0.000549


62
0.25
0.000456


63
0.636
0.000283


64
0.518
0.000495


65
0.773
0.000685


66
0.558
0.000326


67
0.53
0.000326


68
0.386
0.000476


69
0.676
0.000268


70
0.71
0.000616


71
0.754
0.000348


72
0.851
0.000536


73
0.605
0.000426


74
0.356
0.000222


75
0.0122
0.000445


76
0.993
0.000739


77
0.0561
0.00288


78
0.0565
0.0024


79
0.121
0.00697


80
0.228
0.00571


81
0.0155
0.00268


82
0.357
0.00642


83
0.899
0.0023


84
1.67
0.0109


85
4.07
0.00141


86
2.04
0.0119


87
2.05
0.00135


88
2.85
0.00855


89
0.667
0.000383


90
0.204
0.00063


91
0.174
0.00126


92
0.183
0.000881


93
0.389
0.00139


94
0.29
0.000593


95
0.201
0.000991


96
0.192
0.00156


97
0.109
0.000333


98
0.12
0.000367


99
0.119
0.000411


100
0.102
0.000169


101
0.332
0.00173


102
0.385
0.00121


103
0.84
0.00144


104
0.135
0.002


105
0.106
0.000476


106
0.247
0.000201


107
0.0451
0.000492


108
1.77
0.00105


109
0.34
0.000209


110
0.423
0.000174


111
0.263
0.000209


112
0.0465
0.000169


113
0.356
0.000169


114
0.818
0.00111


115
0.243
0.000676


116
0.863
0.00069


117
0.392
0.000436


118
0.0352
0.000234


119
0.942
0.000783


120
0.0739
0.000367


121
0.486
0.000234


122
0.255
0.00476


123
0.133
0.00257


124
1.1
0.00212


125
0.547
0.00209


126
0.102
0.000963


127
0.0522
0.000522


128
0.0307
0.000873


129
0.0116
0.000634


130
0.0532
0.000981


131
0.0152
0.00167


132
0.155
0.0133


133
0.067
0.000709


134
0.303
0.00149


135
0.0738
0.00127


136
0.0727
0.000512


137
0.315
0.00721


138
0.0807
0.000424


139
0.582
0.000173


140
1.34
0.000927


141
2.11
0.000757


142
1.43
0.00305


143
8.71
0.00203


144
9.49
0.00292


145
0.191
0.00108


146
0.261
0.000403


147
0.251
0.00063


148
6.23
0.00135


149
>10
0.00486


150
6.11
0.00349


151
7.15
0.00554


152
3.6
0.00691


153
0.118
0.00188


154
0.194
0.0026


155
3.37
0.0023


156
3.27
0.00318


157
4.14
0.0011


158
0.341
0.00639


159
2.49
0.00216


160
3.22
0.00126


161
1.31
0.00289


162
2.57
0.00209


163
2.1
0.00629


164
2.46
0.00346


165
1.53
0.00161


166
1.43
0.00181


167
1.73
0.00252


168
1.11
0.000951


169
0.375
0.00425


170
3.36
0.00225


171
2.17
0.00251


172
2.21
0.00355


173
1.51
0.00124


174
0.0283
0.000169


175
0.697
0.0009


176
0.0606
0.000414


177
0.0201
0.000169


178
0.0143
0.000169


179
0.0581
0.000445


180
0.584
0.000266


181
0.349
0.000283


182
0.139
0.0004


183
1.05
0.0018


184
4.34
0.00254


185
>10
0.00186


186
0.0657
0.000347


187
0.549
0.000172


188
>10
0.00509


189
0.192
0.0111


190
0.4
0.00457


191
0.821
0.00609


192
0.238
0.000242


193
0.516
0.000266


194
0.0323
0.00024


195
0.0247
0.000251


196
0.358
0.000169


197
1.57
0.000505


198
0.0325
0.000225


199
0.00976
0.000311


200
0.063
0.000482


201
0.0466
0.000281


202
0.216
0.000355


203
0.0137
0.00021


204
4.83
0.000773


205
1.06
0.000358


206
0.0257
0.000263


207
1.51
0.000282


208
0.404
0.000169


209
0.811
0.000988


210
0.469
0.000363


211
1.66
0.000453


212
0.0448
0.00021


213
0.116
0.000271


214
0.641
0.00128


215
2.01
0.00304


216
0.118
0.00019


217
0.22
0.0002


218
0.123
0.000169


219
0.0794
0.000903


220
0.0742
0.000278


221
0.12
0.000352


222
0.112
0.000192


223
0.109
0.000354


224
0.233
0.000555


225
0.155
0.000673


226
0.113
0.000608


227
0.0162
0.000273


228
0.0494
0.000238


229
0.0136
0.000398


230
0.294
0.000169


231
0.817
0.000546


232
0.396
0.000277


233
0.495
0.000401


234
0.904
0.000736


235
0.494
0.000369


236
0.604
0.000243


237
0.451
0.000285


238
0.123
0.000187


239
0.308
0.000771


240
7.35
0.00875


241
0.0674
0.000169


242
0.0571
0.000169


243
0.169
0.000169


244
>10
0.00169


245
2.89
0.000502


246
0.0732
0.00022


247
0.0627
0.000275


248
0.0658
0.000169


249
0.817
0.00072


250
0.0205
0.00023


251
2.2
0.00063


252
0.0374
0.000274


253
0.0144
0.000229


254
0.0313
0.000306


255
8.19
0.00222


256
0.126
0.000266


257
0.101
0.000344


258
0.113
0.000558


259
0.0266
0.000169


260
0.0465
0.000351


261
0.0627
0.000231


262
0.00367
0.000221


263
0.0486
0.000247


264
0.0404
0.000412


265
0.0331
0.000266


266
0.12
0.000333


267
0.0543
0.000291


268
0.755
0.000169


269
0.0412
0.000169


270
0.0609
0.000991


271
0.0517
0.000169


272
0.0272
0.000417


273
0.0493
0.000555


274
0.0178
0.000196


275
0.0123
0.00043


276
0.107
0.000468


277
0.103
0.000667


278
0.102
0.000621


279
0.0688
0.000437


280
0.0113
0.000213


281
0.0055
0.000214


282
0.0765
0.000297


283
0.0632
0.000264


284
0.00796
0.000169


285
0.0826
0.000593


286
0.12
0.000412


287
0.0673
0.000351


288
0.0495
0.000568


289
0.155
0.000286


290
0.415
0.00096


291
0.159
0.000449


292
1.54
0.00115


293
0.0273
0.000169


294
0.0447
0.000169


295
0.0561
0.000292


296
0.067
0.000226


297
0.177
0.000286


298
3.41
0.000557


299
0.172
0.000283


300
0.0614
0.000169


301
0.288
0.000301


302
0.16
0.000435


303
0.00999
0.000169


304
0.0662
0.000169


305
0.494
0.000449


306
0.144
0.000169


307
0.0508
0.000169


308
0.306
0.000169


309
0.117
0.000169


310
0.564
0.000217


311
0.289
0.000274


312
0.165
0.000243


313
0.531
0.00036


314
1.98
0.000581


315
0.231
0.00032


316
0.0421
0.000169


317
0.317
0.000282


318
0.0416
0.000228


319
0.466
0.000192


320
0.0963
0.000208


321
3.16
0.000792


322
6.04
0.0341


323
1.4
0.000232


324
0.981
0.000752


325
0.18
0.000278


326
2.35
0.0013


327
1.32
0.000558


328
0.068
0.000169


329
0.0308
0.000169


330
0.32
0.000432


331
0.383
0.000416


332
0.18
0.000297


333
0.583
0.000346


334
0.0809
0.000345


335
0.632
0.000354


336
0.334
0.000264


337
0.497
0.000205


338
0.609
0.000394


339
>10
0.000797


340
>10
0.000817


341
>10
0.000719


342
>10
0.000454


343
>10
0.000456


344
0.036
0.000169


345
0.201
0.00027


346
3.11
0.000548


347
4.73
0.000667


348
>10
0.00152


349
4.11
0.000736


350
>10
0.000795


351
8.39
0.000792


352
>10
0.00106


353
3.17
0.00047


354
>10
0.000526


355
0.831
0.000169


356
>10
0.000169


357
>10
0.000291


358
1.84
0.00219


359
>10
0.0025


360
0.291
0.000717


361
5.03
0.00194


362
0.143
0.000256


363
0.588
0.000305


364
0.135
0.000172


365
1.34
0.000171


366
0.146
0.000435


367
0.65
0.00018


368
0.602
0.000317


369
0.429
0.000337


370
0.0476
0.000175


371
1.44
0.000298


372
2.44
0.00046


373
3.04
0.00036


374
1.67
0.000292


375
0.986
0.000241


376
1.05
0.000305


377
1.67
0.000275


378
0.897
0.000169


379
0.279
0.00029


380
0.179
0.000251


381
0.0841
0.000259


382
0.119
0.000204


383
0.0495
0.000225


384
0.406
0.000375


385
0.491
0.000539


386
0.283
0.000254


387
0.419
0.000467


388
0.388
0.000506


389
0.584
0.000617


390
0.133
0.000445


391
0.171
0.000227


392
0.814
0.000465


393
>10
0.00437


394
>10
0.00308


395
0.0125
0.000193


396
0.0226
0.00036


397
0.0177
0.000169


398
0.21
0.000792


399
9.5
0.00154


400
0.0812
0.000298


401
0.0126
0.000292


402
0.0548
0.000327


403
1.55
0.000847


404
2.55
0.00088


405
0.0784
0.000214


406
1.14
0.000505


407
0.22
0.000659


408
0.276
0.000725


409
>10
0.48


410
0.0207
0.000169


411
1.87
0.000556


412
1.25
0.000424


413
0.805
0.000279


414
2.63
0.000307


415
1.62
0.000246


416
2.5
0.000318


417
6.84
0.000264


418
4.75
0.000233


419
2.43
0.000197


420
2.71
0.000226


421
2.45
0.000271


422
1.72
0.000212


423
8.26
0.000338


424
0.988
0.000494


425
0.153
0.000227


426
0.0256
0.000169


427
0.15
0.00027


428
0.0871
0.000258


429
0.129
0.000396


430
0.292
0.000264


431
0.301
0.000276


432
0.304
0.00033


433
0.2
0.000248


434
0.102
0.000169


435
0.163
0.000191


436
1.59
0.000416


437
0.0291
0.000169


438
0.145
0.000427


439
0.453
0.000641


440
0.295
0.00049


441
0.338
0.000324


442
0.301
0.0002


443
0.138
0.000274


444
0.156
0.000244


445
0.11
0.000212


446
0.388
0.000253


447
0.261
0.000232


448
0.175
0.000176


449
0.256
0.000169


450
0.422
0.000244


451
0.4
0.000373


452
0.293
0.000285


453
0.152
0.000258


454
0.405
0.00034


455
0.0167
0.000194


456
0.389
0.000169


457
1.14
0.000487


458
0.94
0.000382


459
0.381
0.00041


460
0.569
0.000307


461
0.459
0.000169


462
0.0591
0.000266


463
0.314
0.000529


464
0.0634
0.000169


465
0.0138
0.000169


466
0.0749
0.000287


467
0.0911
0.000278


468
>10
0.000985


469
>10
0.000432


470
5.58
0.000456


471
3.44
0.000471


472
2.86
0.000334


473
>10
0.00101


474
1.98
0.000362


475
0.00976
0.000169


476
0.0708
0.000194


477
0.0729
0.000235


478
0.192
0.00024


479
0.063
0.000243


480
0.181
0.000342


481
0.0572
0.000176


482
0.0763
0.000259


483
0.13
0.000575


484
0.0795
0.00019


485
0.0956
0.000205


486
0.0917
0.000232


487
0.143
0.000334


488
0.138
0.000544


489
1.22
0.000263


490
0.753
0.000267


491
>10
0.0019


492
>10
0.000863


493
1.29
0.000455


494
7.56
0.000712


495
1.47
0.000399


496
0.199
0.00114


497
0.0242
0.00286


498
0.309
0.000169


499
0.113
0.00038


500
0.181
0.000169


501
0.104
0.000483


502
0.169
0.000385


503
0.0532
0.000277


504
0.185
0.000361


505
0.253
0.000355


506
0.245
0.000407


507
0.121
0.000359


508
0.257
0.000481


509
0.163
0.000384


510
0.142
0.000284


511
0.0653
0.000286


512
0.631
0.000209


513
0.0239
0.000188


514
0.368
0.000249


515
0.18
0.000268


516
0.117
0.000266


517
0.33
0.000264


518
0.234
0.000169


519
0.218
0.000338


520
0.565
0.000301


521
0.413
0.000292


522
0.0581
0.000199


523
0.343
0.000422


524
0.0247
0.000169


525
0.0864
0.000213


526
0.126
0.000275


527
0.141
0.000265


528
0.126
0.000276


529
0.248
0.000283


530
0.378
0.000791


531
0.333
0.000253


532
0.338
0.000178


533
0.101
0.000169


534
0.145
0.000251


535
0.297
0.000325


536
0.0776
0.000202


537
0.461
0.00023


538
0.275
0.000514


539
0.0985
0.00031


540
0.266
0.000305


541
0.175
0.000448


542
0.0351
0.000337


543
1.48
0.000383


544
0.871
0.000437


545
0.109
0.000403


546
0.237
0.0232


547
0.498
0.000423


548
0.397
0.000471


549
0.0812
0.000224


550
0.762
0.000427


551
0.713
0.000392


552
0.184
0.000543


553
0.478
0.000592


554
0.451
0.000837


555
0.427
0.000749


556
0.00543
0.000407


557
0.167
0.000359


558
1.41
0.000352


559
0.681
0.000223


560
0.969
0.000312


561
0.869
0.000335


562
0.218
0.000607


563
0.322
0.00419


564
0.0238
0.00343


565
0.215
0.00538


566
>10
0.216


567
0.403
0.00111


568
0.375
0.000723


569
0.217
0.000669


570
0.0704
0.000751


571
0.0417
0.000494


572
0.0516
0.000403


573
0.0242
0.000403


574
0.0975
0.000505


575
3.25
0.0108


576
0.016
0.000783


577
0.0189
0.000361


578
0.682
0.000775


579
0.488
0.000634


580
1.47
0.000798


581
0.945
0.00109


582
0.711
0.000911


583
1.12
0.000799


584
0.811
0.000756


585
0.641
0.000648


586
0.842
0.00109


587
0.236
0.000917


588
0.684
0.000623


589
0.0161
0.000887


590
0.666
0.000734


591
0.138
0.000761


592
0.0388
0.000603


593
0.767
0.000544


594
0.0227
0.000682


595
0.133
0.000746


596
0.691
0.000909


597
0.232
0.000862


598
0.457
0.000804


599
0.527
0.000786


600
0.51
0.000169


601
0.712
0.000682


602
0.786
0.000887


603
1.03
0.00101


604
0.151
0.000843


605
0.559
0.000886


606
0.281
0.000169


607
0.478
0.000796


608
0.481
0.00051


609
0.598
0.00062


610
0.751
0.000762


611
0.288
0.000621


612
0.706
0.000919


613
0.347
0.000916


614
0.216
0.00067


615
0.544
0.00079


616
0.174
0.00049


617
0.164
0.000645


618
0.5
0.000751


619
0.0793
0.000616


620
0.71
0.001


621
0.114
0.00542


622
0.0294
0.00236


623
1.01
0.0016


624
0.261
0.000627


625
0.795
0.00076


626
0.645
0.000793


627
0.211
0.00071


628
0.706
0.000978


629
0.23
0.000643


630
0.266
0.000563


631
0.616
0.00126


632
0.27
0.000698


633
0.335
0.000707


634
0.353
0.000648


635
0.462
0.000975


636
0.238
0.000915


637
0.36
0.000421


638
0.0166
0.000545


639
0.215
0.000713


640
0.17
0.000817


641
0.0748
0.000684


642
0.454
0.000532


643
0.028
0.000552


644
0.0817
0.00069


645
0.091
0.000474


646
0.195
0.00051


647
0.173
0.000672


648
0.661
0.00106


649
0.203
0.000749


650
0.153
0.00111


651
0.276
0.000715


652
0.535
0.00116


653
0.831
0.000893


654
0.213
0.000945


655
0.23
0.000998


656
0.218
0.000738


657
0.232
0.000589


658
0.137
0.00076


659
0.646
0.00071


660
0.282
0.000693


661
0.462
0.000641


662
0.318
0.000671


663
0.653
0.00107


664
0.214
0.000733


665
0.123
0.000357


666
0.193
0.000855


667
0.226
0.000798


668
0.263
0.0011


669
0.407
0.000807


670
0.062
0.000545


671
0.611
0.00106


672
0.313
0.000504


673
0.452
0.000697


674
0.297
0.000535


675
0.376
0.00207


676
0.126
0.00698


677
0.00177
0.000796


678
0.0412
0.00023


679
0.0228
0.00174


680
0.0371
0.00238


681
0.0276
0.002


682
0.607
0.00158


683
0.154
0.00119


684
0.481
0.00134


685
1.25
0.00136


686
0.959
0.0013


687
0.0973
0.00116


688
1.11
0.00266


689
0.016
0.00132


690
0.0643
0.00122


691
0.169
0.00067


692
0.0839
0.00119


693
0.781
0.00142


694
0.163
0.00112


695
0.0137
0.000621


696
0.272
0.000725


697
0.735
0.000802


698
0.0364
0.000629


699
0.0411
0.000721


700
0.0684
0.00103


701
0.367
0.000856


702
0.568
0.00129


703
0.559
0.000824


704
0.503
0.000777


705
0.876
0.00163


706
0.0841
0.000937


707
0.277
0.000624


708
0.06
0.0009


709
0.0194
0.000473


710
0.0491
0.00125


711
0.0885
0.00111


712
0.0911
0.000907


713
0.0443
0.000689


714
0.168
0.000991


715
0.0659
0.000771


716
0.0502
0.000607


717
0.186
0.000428


718
0.0236
0.000755


719
0.00632
0.000835


720
0.0367
0.000181


721
0.125
0.00121


722
0.0394
0.00101


723
0.154
0.000932


724
0.161
0.000992


725
0.0196
0.000747


726
0.251
0.000534


727
0.166
0.000783


728
0.14
0.000496


729
0.428
0.000765


730
0.489
0.000847


731
0.223
0.000391


732
0.0213
0.000471


733
0.119
0.000712


734
0.0142
0.000605


735
0.646
0.000864


736
3.09
0.00073


737
0.0704
0.000612


738
0.364
0.000705


739
0.0377
0.000672


740
0.0701
0.000403


741
0.068
0.000647


742
0.241
0.000526


743
0.0633
0.000691


744
1.08
0.000806


745
0.994
0.000783


746
0.795
0.000839


747
0.435
0.00175


748
0.558
0.000648


749
0.392
0.00079


750
1.53
0.00154


751
1.24
0.001


752
5.19
0.00077


753
0.403
0.000783


754
0.00492
0.00051


755
0.013
0.00057


756
0.123
0.000609


757
0.0156
0.000705


758
0.132
0.00061


759
0.0285
0.000799


760
0.0289
0.00071


761
0.0944
0.000394


762
0.0301
0.000506


763
0.0485
0.000478


764
0.135
0.000465


765
0.0365
0.000782


766
0.0615
0.000581


767
0.265
0.00064


768
0.0281
0.000672


769
0.0984
0.000705


770
0.0388
0.000735


771
0.0708
0.000573


772
0.0615
0.000828


773
0.0726
0.000773


774
0.103
0.00046


775
0.0519
0.000538


776
0.0215
0.000169


777
0.0394
0.00092


778
0.0276
0.000414


779
0.0142
0.000603


780
0.25
0.000382


781
0.0875
0.000839


782
0.134
0.000466


783
0.0644
0.000907


784
0.0226
0.000455


785
0.0236
0.000638


786
0.0444
0.000484


787
0.055
0.000474


788
0.082
0.000674


789
0.0217
0.000434


790
0.0795
0.000586


791
0.0471
0.00115


792
0.116
0.0005


793
0.0231
0.000398


794
0.029
0.000465


795
0.0896
0.000764


796
0.0917
0.00049


797
0.0972
0.000671


798
0.0957
0.00047


799
0.102
0.000406


800
0.0821
0.000925


801
0.866
0.001


802
0.0359
0.000533


803
0.314
0.00101


804
0.289
0.000445


805
3.92
0.00112


806
2.74
0.000543


807
0.628
0.000509


808
0.0944
0.000568


809
0.0953
0.00063


810
0.481
0.0126


811
0.0998
0.00286


812
0.08
0.00257


813
0.0112
0.00153


814
0.0687
0.00163


815
0.053
0.00193


816
0.0461
0.00158


817
0.0658
0.0016


818
1.52
0.000644


819
0.0199
0.000624


820
0.499
0.00928


821
0.663
0.000284


822
0.104
0.00346


823
0.189
0.000356


824
0.118
0.000566


825
0.0261
0.000538


826
0.00779
0.000897









NAMPT Cell Proliferation Assay

PC3 cells were seeded in 96-well black plates (Corning #3904) at 500 cells/well in 90 μl of RPMI media containing 10% heat-inactivated FBS and incubated overnight at 37° C. and 5% CO2 to allow cells to attach to wells. The following day, test compounds were serially diluted in neat DMSO to 1000× final concentrations prior to dilution with RPMI media to 10× and 1% DMSO. Ten μL of the 10× compounds were then transferred to wells containing cells to produce a dose response of 10-fold dilutions from 10 μM to 1×10−5 μM. Cells were incubated for 5 days at 37° C. and 5% CO2, then cell viability was measured using Cell Titer Glo reagent (Promega #G7571). Percent inhibition values were calculated and fitted to a sigmoidal dose response curves using Assay Explorer software to determine IC50s. To assess whether inhibition of cell viability was due to NAMPT inhibition, the proliferation assay was also performed in the presence of 0.3 mM nicotinamide mononucleotide.


Table 2 shows the results of the cell proliferation assay.












TABLE 2








Cell




Titer-Glo-IC50



Example
(μM)



















1
0.0609



2
>10



3
0.0367



4
0.935



5
0.74



6
6.65



7
0.527



8
0.0702



9
0.649



10
0.331



11
4.53



12
0.213



13
1.17



14
0.644



15
3.97



16
0.325



17
4.96



18
0.36



19
6.63



20
0.102



21
0.899



22
0.142



23
0.0415



24
0.691



25
0.146



26
0.261



27
7.54



28
0.0142



29
0.0439



30
0.0384



31
0.107



32
0.284



33
0.0673



34
0.0383



35
0.0586



36
0.0514



37
0.0347



38
0.0659



39
7.28



40
0.0708



41
0.138



42
1.59



43
7.45



44
1.58



45
2.07



46
6.28



47
0.0648



48
5.32



49
7.04



50
6.14



51
0.083



52
0.00407



53
3.3



54
0.303



55
0.0146



56
0.00886



57
0.00576



58
0.0526



59
0.143



60
0.00958



61
0.00601



62
0.0165



63
0.0168



64
0.0198



65
0.0656



66
0.0115



67
0.0119



68
0.0538



69
0.0166



70
0.0278



71
0.0667



72
0.0659



73
0.0595



74
0.014



75
0.00149



76
0.185



77
0.0142



78
0.0407



79
0.00745



80
0.0194



81
0.0071



82
0.0679



83
0.0243



84
0.762



85
2.61



86
5.72



87
6.58



88
8.11



89
0.113



90
0.0187



91
0.0139



92
0.00948



93
0.00713



94
0.0142



95
0.0106



96
0.00965



97
0.00455



98
0.0194



99
0.0264



100
0.0162



101
0.00244



102
0.013



103
0.0621



104
0.00846



105
0.00661



106
0.0787



107
0.0108



108
7.66



109
0.0522



110
0.202



111
0.0755



112
0.00696



113
0.0933



114
0.142



115
0.00638



116
0.0613



117
0.0639



118
0.0182



119
0.146



120
0.0908



121
0.00391



122
0.172



123
0.00743



124
0.0208



125
0.023



126
0.00396



127
0.00234



128
0.00221



129
0.00274



130
0.00655



131
0.00217



132
0.523



133
0.00216



134
0.00654



135
0.00636



136
0.00305



137
0.225



138
0.00383



139
0.0122



140
0.0655



141
0.0778



142
0.0182



143
0.0808



144
0.187



145
0.00601



146
0.00769



147
0.00669



148
0.0415



149
0.0266



150
0.0362



151
0.0761



152
0.0283



153
0.00373



154
0.00667



155
0.0176



156
0.028



157
0.0292



158
0.191



159
0.233



160
0.915



161
0.635



162
0.0436



163
0.0964



164
0.101



165
0.137



166
0.0971



167
0.104



168
0.208



169
0.0269



170
0.604



171
0.0447



172
0.223



173
0.0501



174
0.00112



175
0.313



176
0.00181



177
0.00169



178
0.00185



179
0.00218



180
0.00912



181
0.00775



182
0.00137



183
0.063



184
0.0651



185
5.05



186
0.00236



187
0.0341



188
6.29



189
0.0293



190
0.0149



191
0.0143



192
0.00185



193
0.0199



194
0.000773



195
0.000966



196
0.00675



197
0.0254



198
0.00184



199
0.000539



200
0.00572



201
0.00189



202
0.00488



203
0.00239



204
1.62



205
0.483



206
0.00131



207
0.739



208
0.0849



209
0.693



210
0.398



211
0.95



212
0.0341



213
0.0397



214
0.289



215
0.686



216
0.00659



217
0.00342



218
0.0711



219
0.00559



220
0.00573



221
0.00782



222
0.00408



223
0.00708



224
0.023



225
0.00927



226
0.00726



227
0.00628



228
0.00856



229
0.00106



230
0.0072



231
0.0351



232
0.00927



233
0.00937



234
0.105



235
0.0555



236
0.0138



237
0.0372



238
0.00257



239
0.0177



240
0.651



241
0.00848



242
0.00756



243
0.028



244
7.04



245
5.5



246
0.00243



247
0.00134



248
0.00242



249
0.0665



250
0.000675



251
1.84



252
0.00191



253
0.000702



254
0.000938



255
4.29



256
0.00984



257
0.0152



258
0.0325



259
0.00254



260
0.00806



261
0.0051



262
0.00187



263
0.00243



264
0.00669



265
0.00159



266
0.606



267
0.665



268
5.54



269
0.0151



270
0.973



271
0.00271



272
0.0156



273
0.00235



274
0.0104



275
0.0239



276
0.0381



277
0.0832



278
0.0517



279
0.869



280
0.013



281
0.0248



282
0.0447



283
0.145



284
0.107



285
0.301



286
0.0194



287
0.0241



288
0.00811



289
0.00933



290
0.0722



291
0.0261



292
7.22



293
0.00774



294
0.00188



295
0.0242



296
0.0115



297
0.0358



298
2.37



299
8.64



300
0.0287



301
0.0258



302
0.0193



303
0.00179



304
0.0188



305
1.17



306
0.0219



307
0.0136



308
0.0295



309
0.0548



310
0.0244



311
0.0191



312
0.065



313
0.82



314
0.395



315
0.72



316
0.00634



317
0.542



318
0.0421



319
0.0293



320
0.171



321
1.13



322
>10



323
0.175



324
0.0547



325
0.0329



326
0.457



327
0.638



328
0.0089



329
0.0124



330
0.0229



331
0.227



332
0.0643



333
0.116



334
0.0219



335
0.0976



336
0.139



337
0.533



338
0.081



339
9.18



340
>10



341
8.3



342
6.73



343
6.53



344
0.00746



345
0.281



346
7.02



347
8.08



348
>10



349
5.51



350
8.17



351
8.11



352
9.8



353
7.51



354
7.49



355
1.94



356
1.02



357
6.74



358
2.26



359
8.77



360
0.663



361
>10



362
0.106



363
7.66



364
0.031



365
0.332



366
0.0215



367
0.601



368
0.0484



369
0.738



370
0.00993



371
0.82



372
0.868



373
0.585



374
0.792



375
>10



376
>10



377
>10



378
>10



379
0.37



380
0.04



381
0.0173



382
0.0838



383
0.0133



384
0.0517



385
0.11



386
0.0424



387
0.0581



388
0.122



389
0.0783



390
0.0803



391
0.0784



392
0.666



393
>10



394
>10



395
0.00634



396
0.0324



397
0.00712



398
0.0736



399
7.68



400
0.712



401
0.0559



402
0.00671



403
0.0545



404
9.41



405
0.0221



406
0.347



407
1.31



408
0.0192



409
10



410
nd



411
4.72



412
0.978



413
0.19



414
0.853



415
0.234



416
0.659



417
0.867



418
0.866



419
0.365



420
0.147



421
0.317



422
0.109



423
0.187



424
0.521



425
0.069



426
0.0064



427
0.0622



428
0.0675



429
0.0186



430
0.0886



431
0.0719



432
0.0363



433
0.0644



434
0.00559



435
0.0204



436
0.762



437
0.00702



438
0.0425



439
0.0375



440




441
0.0072



442
0.0707



443
0.00896



444
0.0699



445
0.0229



446
0.0612



447
0.0125



448
0.0678



449
0.0236



450
0.0701



451
0.0173



452
0.0592



453
0.00921



454
0.0422



455
0.0035



456
0.0496



457
0.194



458
0.183



459
0.0777



460
0.0509



461
0.0314



462
0.00743



463
0.234



464
0.00679



465
0.000319



466
0.00431



467
0.00402



468
2.93



469
3.38



470
0.936



471
6.51



472
0.963



473
7.85



474
0.879



475
0.00692



476
0.00942



477
0.00321



478
0.0312



479
0.00808



480
0.00743



481
0.00579



482
0.00222



483
0.0124



484
0.00959



485
0.0345



486
0.0233



487
0.0833



488
0.0983



489
>10



490
0.0899



491
7.83



492
1.27



493
0.486



494
1.22



495
0.127



496
7.14



497
0.742



498
0.0179



499
0.00219



500
0.0217



501
0.00596



502
0.0165



503
0.00421



504
0.0154



505
0.0305



506
0.0180018



507
0.0032



508
0.0285902



509
0.00747



510
0.0121



511
0.00278



512
0.0179



513
0.0011805



514
0.0308



515
0.0158



516
0.021279



517
0.0722



518
0.0348



519
0.0609



520
0.101



521
0.0935



522
0.00673



523
0.0171



524
0.00246



525
0.00677



526
0.0603



527
0.0598



528
0.024



529
0.227



530
0.0821



531
0.0529



532
0.0927



533
0.0174



534
0.00508



535
0.0285



536
0.00304



537
0.0431



538
0.00333



539
0.00347



540
0.074



541
0.0645



542
0.00289



543
0.386



544
0.647



545
0.0287



546
2.45



547
0.0255558



548
0.0744613



549
0.009417



550
0.1741494



551
0.0550545



552
0.0425577



553
0.103



554
0.177



555
0.0332



556
0.00655



557
0.0374



558
1.17



559
0.0943



560
0.844



561
0.24



562
0.0709



563
5.14



564
0.211



565
0.891



566
>10



567
0.237



568
0.18



569
0.226



570
0.00735



571
0.0229



572
0.00666



573
0.00372



574
0.005201



575
>10



576
.000569



577
0.00215



578
4.6



579
0.758



580
0.212



581
0.0812



582
0.0332



583
0.189



584
0.0587



585
0.0346



586
0.301



587
0.00754



588
0.181



589
0.00131



590
0.189



591
0.0193



592
0.00375



593
0.677



594
0.00111



595
0.00693



596
0.257



597
0.0335



598
0.0166



599
0.0523



600
0.11



601
0.0567



602
0.0486107



603
0.695



604
0.0101



605
0.0661



606
0.0348



607
0.0744



608
0.148



609
0.142



610
0.0744



611
0.0709



612
0.695



613
0.14



614
0.00572



615
0.0188



616
0.0326



617
0.0826



618
0.125



619
0.0033



620
0.131



621
0.0253



622
0.00706



623
0.446



624
0.329



625
0.226



626
0.0807



627
0.0175



628
0.0436



629
0.0652



630
0.0404



631
0.0772



632
0.0323



633
0.012



634
0.0835



635
0.05



636
0.0184



637
0.0811



638
0.00261



639
0.0581



640
0.05



641
0.00999



642
0.0949



643
0.0069



644
0.00408



645
0.034



646
0.13



647
0.00699



648
0.203



649
0.0706



650
0.0583



651
0.0648



652
0.0346



653
0.715



654
0.0679



655
0.0688



656
0.0385



657
0.036



658
0.0608



659
0.223



660
0.0709



661
0.0672



662
0.0934



663
0.09



664
0.0715



665
0.00728



666
0.00518



667
0.0458



668
0.0803



669
0.686



670
0.00992



671
0.684



672
0.08



673
0.122



674
0.0324



675
0.0698



676
0.0787



677
6.13E−04



678
0.0151



679
0.0109



680
0.629



681
0.145



682
0.771



683
0.0361



684
0.32



685
0.074



686
0.0772



687
0.00219



688
5.48



689
0.00721



690
0.0138



691
0.0777



692
0.0198



693
0.652



694
0.0247



695
0.00582



696
0.667



697
0.633



698
0.000670



699
0.00527



700
0.00325



701
0.0761902



702
0.088



703
0.0903



704
0.0915



705
0.0958



706
0.00654



707
0.0741



708
0.00597



709
0.00336



710
0.00276



711
0.00325



712
0.0058



713
0.00286



714
0.0174



715
0.00349



716
0.021



717
0.0724



718
0.00125



719
0.00237



720
0.00582



721
0.0307



722
0.00388



723
0.0716



724
0.0632



725
0.006



726
0.0719



727
0.0582



728
0.021



729
0.0459



730
0.0295



731
0.05



732
0.0059



733
0.0202



734
0.000553



735
0.688



736
8.36



737
0.00405



738
0.0859



739
0.0676



740
0.00813



741
0.0749



742
0.0105



743
0.00681



744
0.505



745
0.632



746
0.116



747
0.942



748
0.0507



749
0.077



750
0.794



751
0.755



752
6.66



753
0.0746



754
0.00125



755
0.00249



756
0.0189



757
0.000435



758
0.0232



759
0.00165



760
0.00119



761
0.0277



762
0.00112



763
0.00231



764
0.0687



765
0.00291



766
0.00636



767
0.0672



768
0.000905



769
0.00526



770
0.006



771
0.00347



772
0.0024



773
0.00953



774
0.00707



775
0.0609



776
0.0021



777
0.00126



778
0.000896



779
0.000499



780
0.0817



781
0.00727



782
0.0247



783
0.0098



784
0.00238



785
0.000839



786
0.00751



787
0.00675



788
0.00544



789
0.0694



790
0.0026



791
0.000898



792
0.00957



793
0.00102



794
0.000883



795
0.0062



796
0.00465



797
0.00698



798
0.00963



799
0.00696



800
0.00621



801
0.0573



802
0.00583



803
0.0176



804
0.0497



805
7.82



806
1.4



807
0.1



808
0.0011



809
0.0332



810
0.327



811
0.0114



812
0.0388



813
0.00221



814
0.0045



815
0.00589



816
0.00482



817
0.00927



818
0.716



819
0.013



820
0.802



821
0.192



822
0.0711



823
0.00462



824
0.0124



825
0.00106



826
0.00679



827
0.000625



828
0.00644



829
0.00177



830
0.000269



831
0.000886



832
0.0101



833
0.07



834
0.0127



835
0.00395



836
0.0683



837
0.00277



838
0.0027



839
0.000607



840
0.00275



841
0.00613



842
0.0714



843
0.0172



844
0.0148172



845
0.00389



846
0.0744



847
0.0936



848
0.0292



849
0.0636



850
0.054



851
0.133



852
0.00832



853
0.00996



854
0.000414



855
0.111



856
0.657



857
0.00155



858
0.00059



859
0.0104



860
0.00824



861
0.000574



862
0.000780



863
0.000642



864
0.0672



865
0.000861



866
0.000525



867
0.0687



868
0.0869



869
6.87



870
0.994



871
7.3



872
>10



873
3.87



874
6.65



875
1.14



876
0.0477



877
>10



878
>10



879
0.0633



880
0.75



881
8.49



882
>10



883
0.000220



884
0.000968



885
0.005333



886
0.000194



887
0.000214



888
0.000494



889
0.651



890
0.0318



891
0.0872



892
0.00676



893
0.000662



894
0.202



895
0.73



896
1.58



897
0.716



898
0.223



899
0.181



900
0.0174



901
0.865



902
0.0108



903
0.0352



904
0.282



905
0.000994



906
0.00417



907
0.00709



908
0.0112



909
7.21



910
>10



911
0.0425



912
0.008725



913
0.0144



914
0.0772



915
0.174



916
0.00673



917
0.00679



918
0.233



919
0.101



920
0.00794



921
0.157



922
0.00995



923
0.00458



924
0.018



925
0.00206



926
0.00969



927
0.00713



928
0.106



929
0.0247



930
0.00209



931
0.00677



932
0.0303



933
0.0717



934
0.00638



935
0.0103



936
0.0325



937
0.0809



938
0.00627



939
>10



940
0.000691



941
0.000519



942
0.00102



943
0.0244



944
0.00336



945
0.00238



946
0.00594



947
0.00328



948
0.00539



949
0.0254



950
0.634



951
0.0639



952
0.0103



953
0.00235



954
0.00276



955
0.00256



956
0.00883



957
0.00351



958
0.0214



959
0.00976



960
0.00613



961
0.00894



962
0.0161



963
0.0195



964
0.00622



965
0.00831



966
0.00209



967
0.00396



968
0.00177



969
0.00636



970
0.0109



971
0.0226



972
0.0289



973
0.0218



974
0.0287



975
0.0503



976
0.0349



977
0.00265



978
0.00202



979
0.0757



980
0.0294



981
0.00654



982
0.1



983
0.724



984
0.0554



985
0.0283



986
0.0214



987
0.543



988
0.0601



989
0.0682



990
0.0179



991
0.0669



992
0.584



993
0.074



994
0.0121



995
0.0108



996
0.062



997
0.0194



998
0.123



999
0.684



1000
0.0818



1001
0.0953



1002
0.154



1003
0.00496



1004
0.0567



1005
0.0747



1006
0.0737



1007
0.0373



1008
0.00294



1009
0.0012



1010
0.0058



1011
0.00197



1012
0.00836



1013
0.00232



1014
0.00207



1015
0.00168



1016
0.00219



1017
0.00229



1018
0.00164



1019
0.00198



1020
0.000901



1021
0.00111



1022
0.00293



1023
0.00687



1024
0.00352



1025
0.000808



1026
0.00156



1027
0.00228



1028
0.00736



1029
0.000272



1030
0.002040



1031
0.00773



1032
0.00888



1033
0.00197



1034
0.00629



1035
0.00304



1036
0.016



1037
0.00776



1038
0.00784



1039
0.00687



1040
0.0134



1041
0.00241



1042
0.00359



1043
0.0104



1044
0.000892



1045
0.00669



1046
0.00461



1047
0.000205



1048
0.00827



1049
0.00239



1050
0.0234



1051
0.000313



1052
0.0271



1053
0.00341



1054
0.026



1055
0.00438



1056
0.0013



1057
0.0258



1058
0.00249



1059
0.0164



1060
0.00229



1061
0.00784



1062
0.017



1063
0.00189



1064
0.00412



1065
0.00143



1066
0.0057



1067
0.37



1068
0.00577



1069
0.00123



1070
0.000857



1071
0.000473



1072
0.00624



1073
0.00388



1074
0.0144



1075
0.00762



1076
0.0057



1077
0.0691



1078
0.00761



1079
0.0182



1080
0.00341



1081
0.195



1082
0.00218



1083
0.000920



1084
0.0148



1085
0.0256



1086
0.00993



1087
0.00168



1088
0.0344



1089
0.00827



1090
0.00542



1091
0.00419



1092
0.0177



1093
0.565



1094
0.0688



1095
0.00445



1096
0.00207



1097
0.0647



1098
0.00955



1099
0.0156



1100
0.0087



1101
0.00206



1102
0.00177



1103
0.00424



1104
0.00696



1105
0.0026



1106
0.0275



1107
0.00226



1108
0.0201



1109
0.00921



1110
0.111



1111
0.062



1112
0.0164



1113
0.0231



1114
0.0218



1115
0.0212



1116
0.00619



1117
0.0657



1118
0.00418



1119
0.00667



1120
0.00237



1121
0.00842



1122
0.00996



1123
0.00711



1124
0.000344



1125
0.00477



1126
0.00236



1127
0.00299



1128
0.00605



1129
0.00805



1130
0.00296



1131
0.0344



1132
0.00896



1133
0.001



1134
0.00551



1135
0.00423



1136
0.00302



1137
0.000277



1138
0.00385



1139
0.00141



1140
0.00584



1141
0.0022



1142
0.0029



1143
0.0174



1144
0.0096



1145
0.00704



1146
0.00188



1147
0.00283



1148
0.00272



1149
0.00262



1150
0.0641



1151
0.00778



1152
0.00308



1153
0.00172



1154
0.17043



1156
0.0354



1157
0.0531



1158
0.00204



1159
0.01740



1160
0.01630



1161
0.061



1162
0.0618



1163
0.0027



1164
0.158



1165
0.577



1166
0.0261










Compounds which inhibit NAMPT are useful for treating diseases in which activation of NF-KB is implicated. Such methods are useful in the treatment of a variety of diseases including inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukaemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia.


Involvement of NAMPT in the treatment of cancer is described in WO 97/48696. Involvement of NAMPT in immuno-supression is described in WO 97/48397. Involvement of NAMPT for the treatment of diseases involving angiogenesis is described in WO 2003/80054. Involvement of NAMPT for the treatment of rheumatoid arthritis and septic shock is described in WO 2008/025857. Involvement of NAMPT for the prophlaxis and treatment of ischaemia is described in WO 2009/109610.


Cancers include, but are not limited to, hematologic and solid tumor types such as acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute t-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer (including estrogen-receptor positive breast cancer), bronchogenic carcinoma, Burkitt's lymphoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, gastric carcinoma, germ cell testicular cancer, gestational trophobalstic disease, glioblastoma, head and neck cancer, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, liposarcoma, lung cancer (including small cell lung cancer and non-small cell lung cancer), lymphangioendothelio-sarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin's lymphoma and non-Hodgkin's lymphoma), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, leukemia, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, peripheral T-cell lymphoma, pinealoma, polycythemia vera, prostate cancer (including hormone-insensitive (refractory) prostate cancer), rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, testicular cancer (including germ cell testicular cancer), thyroid cancer, Waldenström's macroglobulinemia, testicular tumors, uterine cancer, Wilms' tumor and the like.


Schemes and Experimentals


The following abbreviations have the meanings indicated. ADDP means 1,1′-(azodicarbonyl)dipiperidine; AD-mix-β means a mixture of (DHQD)2PHAL, K3Fe(CN)6, K2CO3, and K2SO4; 9-BBN means 9-borabicyclo(3.3.1)nonane; Boc means tert-butoxycarbonyl; (DHQD)2PHAL means hydroquinidine 1,4-phthalazinediyl diethyl ether; DBU means 1,8-diazabicyclo[5.4.0]undec-7-ene; DIBAL means diisobutylaluminum hydride; DIEA means diisopropylethylamine; DMAP means N,N-dimethylaminopyridine; DMF means N,N-dimethylformamide; dmpe means 1,2-bis(dimethylphosphino)ethane; DMSO means dimethylsulfoxide; dppb means 1,4-bis(diphenylphosphino)-butane; dppe means 1,2-bis(diphenylphosphino)ethane; dppf means 1,1′-bis(diphenylphosphino)ferrocene; dppm means 1,1-bis(diphenylphosphino)methane; EDAC.HCl means 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; Fmoc means fluorenylmethoxycarbonyl; HATU means O-(7-azabenzotriazol-1-yl)-N,N′N′N′-tetramethyluronium hexafluorophosphate; HMPA means hexamethylphosphoramide; IPA means isopropyl alcohol; MP-BH3 means macroporous triethylammonium methylpolystyrene cyanoborohydride; TEA means triethylamine; TFA means trifluoroacetic acid; THF means tetrahydrofuran; NCS means N-chlorosuccinimide; NMM means N-methylmorpholine; NMP means N-methylpyrrolidine; PPh3 means triphenylphosphine.


The following schemes are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. Compounds of this invention may be made by synthetic chemical processes, examples of which are shown herein. It is meant to be understood that the order of the steps in the processes may be varied, that reagents, solvents and reaction conditions may be substituted for those specifically mentioned, and that vulnerable moieties may be protected and deprotected, as necessary.


Schemes




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As shown in Scheme 1, compounds of formula (1), wherein R4 is as described herein, can be reacted with 4-nitrobenzoic acid in the presence of a base such as but not limited to N-methylmorpholine, an ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate, and a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, to provide compounds of formula (2). The reaction is typically performed at ambient temperature in a solvent such as but not limited to dimethylformamide. Compounds of formula (3) can be prepared by reacting compounds of formula (2) with hydrogen in the presence of palladium on carbon. The reaction is typically performed at ambient temperature in a solvent such as but not limited to methanol. Compounds of formula (3) can be reacted with compounds of formula (4) wherein X and Z are as described herein, to provide compounds of formula (5). The reaction is typically performed in the presence of bis(2,5-dioxopyrrolidin-1-yl)carbonate and a base such as but not limited to pyridine. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N-methyl-2-pyrrolidinone.


Alternatively, Compounds of formula (3) can be reacted with compounds of formula (6) wherein X is as described herein, to provide compounds of formula (7). The reaction is typically performed in the presence of bis(2,5-dioxopyrrolidin-1-yl)carbonate and a base such as but not limited to pyridine. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N-methyl-2-pyrrolidinone.




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Compounds of formula (8), wherein IV is as described herein for substituents on the R3 phenyl, can be reacted with compounds of formula (9), wherein X and Z are as described herein, to provide compounds of formula (10). The reaction is typically performed in the presence of a base such as but not limited to N-methylmorpholine, an ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate, and a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. The reaction is typically performed at ambient temperature in a solvent such as but not limited to dimethylformamide.


Similarly, compounds of formula (8), wherein Rx is as described herein for substituents on the R3 phenyl, can be reacted with compounds of formula (11), wherein X is as described herein, to provide compounds of formula (12). The reaction is typically performed in the presence of a base such as but not limited to N-methylmorpholine, an ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate, and a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. The reaction is typically performed at ambient temperature in a solvent such as but not limited to dimethylformamide.




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As shown in Scheme 3, compounds of formula (13), wherein R3 is as described herein, can be reacted with compounds of formula (11), wherein X is as described herein, in the presence of bis(2,5-dioxopyrrolidin-1-yl)carbonate and a base such as but not limited to pyridine to provide compounds of formula (14). The reaction is typically performed at ambient temperature in a solvent such as but not limited to N-methyl-2-pyrrolidinone.


Alternatively, compounds of formula (13), wherein R3 is as described herein, can be reacted with compounds of formula (9), wherein X and Z are as described herein, in the presence of bis(2,5-dioxopyrrolidin-1-yl)carbonate and a base such as but not limited to pyridine to provide compounds of formula (14). The reaction is typically performed at ambient temperature in a solvent such as but not limited to N-methyl-2-pyrrolidinone.




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2-Bromo-5-thiazolecarboxylic acid can be reacted with compounds of formula (9), wherein X and Z are as described herein, in the presence of a base such as but not limited to N-methylmorpholine, an ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate, and a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, to provide compounds of formula (16). The reaction is typically performed at ambient temperature in a solvent such as but not limited to dimethylformamide. Compounds of formula (16) can be reacted with amines of formula (1) wherein R4 is as described herein, to provide compounds of formula (17). The reaction is typically performed at an elevated temperature in a solvent such as but not limited to acetonitrile and may be performed in a microwave oven. Compounds of formula (19), which are representative of the compounds of this invention, can be prepared by reacting compounds of formula (17) with compounds of formula (18), wherein R4 is as described herein, in the presence of a base such as but not limited to diisopropylethylamine. The reaction is typically performed at ambient temperature in a solvent such as but not limited to tetrahydrofuran. Alternatively, compounds of formula (17) can be reacted with amines of formula (4), wherein R4 is as described herein, to provide compounds of formula (20), which are representative of the compounds of Formula (I). The reaction is typically performed in the presence of bis(2,5-dioxopyrrolidin-1-yl)carbonate and a base such as but not limited to pyridine. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N-methyl-2-pyrrolidinone.




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As shown in Scheme 5, compounds of formula (16), which can be prepared as described in Scheme 4 and wherein X and Z are as described herein, can be reacted with suitable boronic acids (or the equivalent boronic ester) of formula (21) wherein R4 is as described herein, under Suzuki coupling conditions known to those skilled in the art and widely available in the literature, to provide compounds of formula (22), which are representative of the compounds of Formula (I).


EXAMPLES

The following examples are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. Each exemplified compound and intermediate was named using ACD/ChemSketch Version 12.5 (20 Apr. 2011) or (3 Sep. 2012), Advanced Chemistry Development Inc., Toronto, Ontario), or ChemDraw® Ver. 9.0.7 (CambridgeSoft, Cambridge, Mass.).


Experimentals
Example 1
4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide
Example 1A
N-isopentyl-4-nitrobenzamide

4-Nitrobenzoic acid (0.8 g, 4.79 mmol) and 1-hydroxybenzotriazole hydrate (1.1 g, 7.18 mmol) in dimethylformamide (20 mL) was treated with N-methylmorpholine (1.8 mL, 16.75 mmol) and 3-methylbutan-1-amine (0.724 mL, 6.22 mmol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.38 g, 7.18 mmol). The reaction mixture was stirred at room temperature for 17 hours. Water was added and the resulting suspension was stirred for 2 hours. The suspension was filtered and the solid collected was washed with water and dried to provide the title compound.


Example 1B
4-amino-N-isopentylbenzamide

N-Isopentyl-4-nitrobenzamide (1 g, 4.23 mmol) and methanol (40 ml) were added to palladium on carbon (0.200 g, 1.879 mmol) in a 250 mL SS pressure bottle and the mixture was stirred for 6 hours with hydrogen at 30 psi and room temperature. The mixture was filtered through a nylon membrane and concentrated to provide the title compound.


Example 1C
4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide

A solution of 4-amino-N-isopentylbenzamide (0.05 g, 0.242 mmol), bis(2,5-dioxopyrrolidin-1-yl)carbonate (0.078 g, 0.303 mmol) and pyridine (0.020 ml, 0.242 mmol) in N-methyl-2-pyrrolidinone (0.6 mL) was stirred at room temperature for 1 hour. Diisopropylethylamine (0.127 ml, 0.727 mmol) was added followed by addition of a solution of imidazo[1,2-a]pyridin-6-amine (0.041 g, 0.279 mmol) in N-methyl-2-pyrrolidinone (0.6 mL) dropwise by syringe over 5 minutes. The reaction mixture was stirred for 16 hours at room temperature and the mixture was treated with water. The resulting suspension was stirred for 5 minutes and filtered with water washes. Vacuum drying and reverse phase chromatography provided the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04-8.93 (m, 2H), 8.76 (bs, 1H), 8.24 (t, J=5.5 Hz, 1H), 7.96 (s, 1H), 7.79 (d, J=8.7 Hz, 2H), 7.58-7.45 (m, 4H), 7.09 (dd, J=9.6, 2.0 Hz, 1H), 3.33-3.20 (m, 2H), 1.68-1.52 (m, 1H), 1.46-1.35 (m, 2H), 0.90 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 366 (M+H)+.


Example 2
4-[(imidazo[1,2-a]pyridin-7-ylcarbamoyl)amino]-N-(3-methylbutyl)benzamide

The title compound was prepared as described in Example 1C, substituting imidazo[1,2-a]pyridin-7-amine for imidazo[1,2-a]pyridin-6-amine. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04 (m, 2H), 8.42 (dd, J=7.5, 0.6 Hz, 1H), 8.25 (t, J=5.5 Hz, 1H), 7.78 (m, 4H), 7.53 (d, J=8.7 Hz, 2H), 7.42 (d, J=1.2 Hz, 1H), 6.90 (dd, J=7.3, 2.1 Hz, 1H), 3.30-3.21 (m, 2H), 1.69-1.54 (m, 1H), 1.47-2.36 (m, 2H), 0.91 (d, J=6.5 Hz, 6H); MS (ESI(+)) m/e 366 (M+H)+.


Example 3
2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide
Example 3A
1-(imidazo[1,2-a]pyridin-6-yl)-3-(4-nitrophenyl)urea

A 0° C. solution of imidazo[1,2-a]pyridin-6-amine (1 g, 7.21 mmol), N-ethyl-N-isopropylpropan-2-amine (2.51 ml, 14.42 mmol) and dimethylformamide (21.85 ml) was treated with a solution of 1-isocyanato-4-nitrobenzene (1.313 g, 8.00 mmol) in tetrahydrofuran (10.92 ml) which was added dropwise via syringe over 5 minutes. The reaction mixture was allowed to stir at room temperature for 6 hours, and water was added. The suspension was filtered with water washes to give the title compound after vacuum drying.


Example 3B
1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-6-yl)urea

The title compound was prepared as described in Example 1B, substituting 1-(imidazo[1,2-a]pyridin-6-yl)-3-(4-nitrophenyl)urea for N-isopentyl-4-nitrobenzamide.


Example 3C
2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}acetamide

The title compound was prepared as described in Example 1A, substituting 1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-6-yl)urea for 3-methylbutan-1-amine and 2-cyclopentylacetic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6, Temp=90° C.) δ ppm 9.73 (bs, 1H), 8.96 (m, 1H), 8.66 (s, 1H), 8.62 (s, 1H), 7.95 (s, 1H), 7.57-7.44 (m, 4H), 7.37 (d, J=8.9 Hz, 2H), 7.07 (dd, J=9.6, 2.0 Hz, 1H), 2.29-2.15 (m, 3H), 1.82-1.68 (m, 2H), 1.68-1.45 (m, 4H), 1.29-1.07 (m, 2H); MS (ESI(+)) m/e 378 (M+H)+.


Table 1.


The following Examples were prepared essentially as described in Example 3, substituting the appropriate carboxylic acid in Example 1C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.















Ex
Name

1H NMR

MS







26
N-{4-[(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.49 (bs, 1H),
m/e



ylcarbamoyl)amino]phenyl}-
8.84 (m, 1H), 8.44 (m, 2H), 7.85 (s,
380 (M + H)+



2-(tetrahydrofuran-3-
1H), 7.52-7.44 (m, 4H),



yl)acetamide
7.39-7.29 (m, 2H), 7.09 (dd, J = 9.6, 2.1 Hz,




1H), 3.83-3.72 (m, 2H),




3.68-3.62 (m, 1H), 3.38-3.33 (m, 1H),




2.57 (m, 1H), 2.40-2.33 (m, 2H),




2.08-1.95 (m, 1H), 1.62-1.52 (m, 1H)


27
N-{4-[imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ

(ESI(+))



a]pyridin-6-
ppm δ 9.81 (s, 1H), 8.98-8.93 (m,
m/e



ylcarbamoyl)amino]phenyl}acetamide
1H), 8.70-8.62 (m, 2H),
310 (M + H)+




7.96-7.93 (m, 1H), 7.53-7.45 (m, 4H),




7.41-7.33 (m, 2H), 7.07 (dd, J = 9.5, 2.0 Hz,




1H), 2.01 (s, 3H)


39
2-ethoxy-N-{4-

1H NMR (400 MHz, DMSO-d6,

(ESI(+))



[(imidazo[1,2-a]pyridin-6-
Temp = 90° C.) δ ppm 9.57 (s, 1H),
m/e



ylcarbamoyl)amino]phenyl}acetamide
8.96 (m, 1H), 8.69 (s, 1H), 8.64 (s, 1H),
354 (M + H)+




7.95 (s, 1H), 7.60-7.48 (m, 4H),




7.42-7.37 (m, 2H), 7.07 (dd, J = 9.6,




2.0 Hz, 1H), 4.00 (s, 2H), 3.56 (q, J = 7.0 Hz,




2H), 1.19 (t, J = 7.0 Hz, 3H)


40
N-{4-[imidazo[1,2-

1H NMR (400 MHz, DMSO-d6,) δ

(ESI(+))



a]pyridin-6-
ppm 9.79 (s, 1H), 8.98-8.93 (m,
m/e



ylcarbamoyl)amino]phenyl}-
1H), 8.67 (s, 1H), 8.63 (s, 1H),
394 (M + H)+



2-(tetrahydro-2H-pyran-4-
7.97-7.93 (m, 1H), 7.54-7.46 (m, 4H),



yl)acetamide
7.40-7.34 (m, 2H), 7.07 (dd, J = 9.5,




2.0 Hz, 1H), 3.87-3.79 (m, 2H),




3.34-3.26 (m, 2H), 2.25-2.19 (m,




2H), 2.07-1.91 (m, 1H),




1.63-1.54 (m, 2H), 1.31-1.17 (m, 2H)


41
N-{4-[imidazo[1,2-

1H NMR (400 MHz, DMSO-d6,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.35 (bs, 1H),
m/e



ylcarbamoyl)amino]phenyl}-
8.85 (m, 1H), 8.50-8.30 (M, 2H),
395 (M + H)+



2-(morpholin-4-
7.86 (s, 1H), 7.55-7.43 (m, 4H),



yl)acetamide
7.41-7.34 (m, 2H), 7.09 (dd, J = 9.5,




2.0 Hz, 1H), 3.68-3.60 (m, 4H),




3.09 (s, 2H), 2.56-2.51 (m, 4H)


42
N-{4-[(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}-

384 (M + H)+



2-(2-



methoxyethoxy)acetamide


43
N-{4-[imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}-

368 (M + H)+



3-methoxy-2-



methylpropanamide


44
N-{4-[imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}butanamide

338 (M + H)+


45
4,4,4-trifluoro-N-{4-

(ESI(+))



[(imidazo[1,2-a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}butanamide

392 (M + H)+


46
-{4-[imidazo[1,2-a]pyridin-

(ESI(+))



6-

m/e



ylcarbamoyl)amino]phenyl}tetrahydro-

380 (M + H)+



2H-pyran-4-



carboxamide


47
N-{4-[(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}-

366 (M + H)+



4-methylpentanamide


48
N-{4-[imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}-

393 (M + H)+



1-methylpiperidine-4-



carboxamide


49
N-{4-[imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}tetrahydro-

428 (M + H)+



2H-thiopyran-4-



carboxamide 1,1-dioxide


50
N-{4-[imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylcarbamoyl)amino]phenyl}-

382 (M + H)+



1,4-dioxane-2-carboxamide









Example 4
4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenylethyl)benzamide
Example 4A
methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate

The title compound was prepared as described in Example 3A, substituting methyl 4-isocyanatobenzoate for 1-isocyanato-4-nitrobenzene.


Example 4B
4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoic acid

A solution of methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate (2.1 g, 6.77 mmol) in tetrahydrofuran (18.05 ml) and methanol (9.02 ml) was treated with 2N lithium hydroxide (13.53 ml, 27.1 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The mixture was concentrated, redissolved in 225 mL water and acidified to pH 4 with 3N hydrochloric acid. The suspension was filtered with water washes to give the title compound after vacuum drying.


Example 4C
4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]-N-(2-phenylethyl)benzamide

The title compound was prepared as described in Example 1A, substituting 2-phenylethanamine for 3-methylbutan-1-amine and 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6/D2O, Temp=90° C.) δ ppm 9.33 (dd, J=1.9, 0.8 Hz, 1H), 8.32 (d, J=1.8 Hz, 1H), 8.05 (d, J=2.0 Hz, 1H), 7.90 (d, J=9.7 Hz, 1H), 7.85-7.74 (m, 3H), 7.61-7.51 (m, 2H), 7.35-7.20 (m, 5H), 3.49 (dd, J=8.1, 6.9 Hz, 2H), 2.94-2.79 (m, 2H); MS (ESI(+)) m/e 400 (M+H)+.


Table 2.


The following Examples were prepared essentially as described in Example 4, substituting the appropriate amine in Example 4C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.















Ex
Name

1H NMR

MS


















5
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.37 (dd, J = 2.0, 0.9 Hz,
m/e



ylcarbamoyl)amino]-
1H), 8.36 (d, J = 2.1 Hz, 1H), 8.10 (d, J = 2.1 Hz,
409 (M + H)+



N-[2-
1H), 7.94 (d, J = 9.6 Hz, 1H),



(morpholin-4-
7.88-7.78 (m, 3H), 7.71-7.57 (m, 2H), 4.02 (d, J = 11.3 Hz,



yl)ethyl]benzamide
2H), 3.66 (dd, J = 16.1, 10.0 Hz, 4H),




3.56 (d, J = 11.3 Hz, 2H), 3.33 (t, J = 6.1 Hz, 2H),




3.17 (d, J = 13.5 Hz, 2H), 2.70 (s, 2H)


6
N-(1-hydroxy-2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



methylpropan-2-
Temp = 90° C.) δ ppm 9.36 (t, J = 6.6 Hz, 1H),
m/e



yl)-4-
8.34 (d, J = 1.9 Hz, 1H), 8.09 (dd, J = 10.9, 5.4 Hz,
368 (M + H)+



[(imidazo[1,2-
1H), 7.90 (t, J = 10.7 Hz, 1H),



a]pyridin-6-
7.85-7.73 (m, 3H), 7.56 (dd, J = 12.5, 5.6 Hz, 2H), 3.51 (s,



ylcarbamoyl)amino]benzamide
2H), 1.49-1.23 (m, 6H)


7
N-benzyl-4-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



[(imidazo[1,2-
Temp = 90° C.) δ ppm 9.38-9.29 (m, 1H),
m/e



a]pyridin-6-
8.33 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H),
386 (M + H)+



ylcarbamoyl)amino]benzamide
7.96-7.85 (m, 3H), 7.77 (td, J = 9.4, 1.5 Hz,




1H), 7.66-7.51 (m, 2H), 7.38-7.31 (m, 4H),




7.32-7.19 (m, 1H), 4.48 (s, 2H)


8
N-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



(cyclopentylmethyl)-
Temp = 90° C.) δ ppm 9.41-9.31 (m, 1H),
m/e



4-
8.34 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H),
378 (M + H)+



[(imidazo[1,2-
7.91 (d, J = 8.9 Hz, 1H), 7.86-7.73 (m, 3H),



a]pyridin-6-
7.63-7.51 (m, 2H), 3.19 (d, J = 7.4 Hz, 2H),



ylcarbamoyl)amino]benzamide
2.24-2.01 (m, 1H), 1.68 (dt, J = 11.6, 7.2 Hz,




2H), 1.64-1.57 (m, 2H), 1.57-1.42 (m, 2H),




1.37-1.14 (m, 2H)


9
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.36 (d, J = 1.4 Hz, 1H),
m/e



ylcarbamoyl)amino]-
8.35 (d, J = 2.0 Hz, 1H), 8.10 (d, J = 2.1 Hz,
421 (M + H)+



N-[3-
1H), 7.94 (d, J = 9.7 Hz, 1H), 7.88-7.80 (m,



(piperidin-1-
3H), 7.66-7.53 (m, 2H), 3.44 (d, J = 12.2 Hz,



yl)propyl]benzamide
2H), 3.34 (t, J = 6.6 Hz, 2H), 3.12-3.02 (m,




2H), 2.97-2.85 (m, 2H), 2.02-1.81 (m, 4H),




1.81-1.58 (m, 4H), 1.51-1.31 (m, 1H)


10
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.36 (dd, J = 6.3, 5.4 Hz,
m/e



ylcarbamoyl)amino]-
1H), 8.35 (d, J = 2.1 Hz, 1H), 8.09 (d, J = 2.0 Hz,
411 (M + H)+



N-(2-
1H), 7.92 (d, J = 9.8 Hz, 1H),



phenoxyethyl)benzamide
7.89-7.80 (m, 3H), 7.63-7.55 (m, 2H), 7.30 (dd, J = 8.4,




7.4 Hz, 2H), 6.95 (dd, J = 11.9, 7.8 Hz, 3H),




4.12 (t, J = 5.8 Hz, 2H), 3.64 (t, J = 5.8 Hz, 2H)


11
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.34 (s, 1H), 8.34 (d, J = 2.0 Hz,
m/e



ylcarbamoyl)amino]-
1H), 8.09 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 9.1 Hz,
393 (M + H)+



N-[2-
1H), 7.88-7.78 (m, 3H), 7.59 (dd, J = 16.4,



(pyrrolidin-1-
8.7 Hz, 2H), 3.59 (dd, J = 15.8, 9.8 Hz,



yl)ethyl]benzamide
4H), 3.33 (t, J = 6.0 Hz, 2H), 3.07 (d, J = 11.0 Hz,




2H), 2.05 (s, 2H), 1.97-1.74 (m, 2H)


12
-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.35 (d, J = 1.3 Hz, 1H),
m/e



ylcarbamoyl)amino]-
8.34 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 2.0 Hz,
382 (M + H)+



N-[2-(propan-
1H), 7.92 (d, J = 9.7 Hz, 1H), 7.88-7.77 (m,



2-
3H), 7.63-7.52 (m, 2H), 3.64-3.55 (m, 1H),



yloxy)ethyl]benzamide
3.51 (dd, J = 20.1, 13.7 Hz, 2H), 3.39 (t, J = 6.2 Hz,




2H), 1.09 (d, J = 6.1 Hz, 6H)


13
N-(2-hydroxy-2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



methylpropyl)-4-
Temp = 90° C.) δ ppm 9.37-9.31 (m, 1H),
m/e



[(imidazo[1,2-
8.33 (d, J = 1.9 Hz, 1H), 8.06 (d, J = 2.0 Hz, 1H),
368 (M + H)+



a]pyridin-6-
7.96-7.88 (m, 1H), 7.88-7.81 (m, 2H),



ylcarbamoyl)amino]benzamide
7.76 (dd, J = 9.6, 1.9 Hz, 1H), 7.65-7.53 (m, 2H),




3.27 (s, 2H), 1.15 (d, J = 27.1 Hz, 6H)


14
N-[2-hydroxy-1-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



(4-
Temp = 90° C.) δ ppm 9.40-9.32 (m, 1H),
m/e



methoxyphenyl)ethyl]-
8.34 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 2.1 Hz, 1H),
446 (M + H)+



4-
7.95-7.86 (m, 3H), 7.81-7.75 (m, 1H),



[(imidazo[1,2-
7.61-7.55 (m, 2H), 7.39-7.26 (m, 2H),



a]pyridin-6-
6.92-6.86 (m, 2H), 5.09-4.96 (m, 1H), 3.72-3.67 (m,



ylcarbamoyl)amino]benzamide
5H), 3.66-3.60 (m, 1H)


15
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.41-9.33 (m, 1H),
m/e



ylcarbamoyl)amino]-
8.35 (d, J = 2.0 Hz, 1H), 8.09 (d, J = 2.1 Hz, 1H),
407 (M + H)+



N-[2-(2-
7.92 (d, J = 9.7 Hz, 1H), 7.82-7.72 (m, 3H),



oxopyrrolidin-1-
7.63-7.51 (m, 2H), 3.50-3.30 (m, 6H),



yl)ethyl]benzamide
2.20 (t, J = 8.1 Hz, 2H), 1.96-1.86 (m, 2H)


16
4-[(imidazo[1,2-
NMR (500 MHz, DMSO-d6/D2O, Temp = 90° C.)
(ESI(+))



a]pyridin-6-
δ ppm 9.39-9.29 (m, 1H), 8.34 (d, J = 2.0 Hz,
m/e



ylcarbamoyl)amino]-
1H), 8.08 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 9.5 Hz,
380 (M + H)+



N-
1H), 7.86-7.77 (m, 3H), 7.63-7.53 (m,



(tetrahydrofuran-
2H), 3.99 (p, J = 6.3 Hz, 1H), 3.64 (dd, J = 14.3,



2-
7.5 Hz, 2H), 3.42-3.24 (m, 2H),



ylmethyl)benzamide
2.03-1.87 (m, 1H), 1.89-1.75 (m, 2H), 1.66-1.52 (m,




1H)


17
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.34 (d, J = 1.3 Hz, 1H),
m/e



ylcarbamoyl)amino]-
8.34 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz,
338 (M + H)+



N-
1H), 7.91 (d, J = 9.6 Hz, 1H), 7.87-7.73 (m,



propylbenzamide
3H), 7.64-7.50 (m, 2H), 3.22 (t, J = 7.1 Hz,




2H), 1.61-1.45 (m, 2H), 0.89 (t, J = 7.4 Hz,




3H)


18
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.35 (d, J = 1.2 Hz, 1H),
m/e



ylcarbamoyl)amino]-
8.35 (d, J = 2.1 Hz, 1H), 8.10 (d, J = 2.1 Hz,
423 (M + H)+



N-[3-
1H), 7.93 (d, J = 9.7 Hz, 1H), 7.85-7.78 (m,



(morpholin-4-
3H), 7.65-7.56 (m, 2H), 4.07-3.96 (m, 2H),



yl)propyl]benzamide
3.66 (t, J = 12.1 Hz, 2H), 3.44 (d, J = 12.4 Hz,




2H), 3.35 (t, J = 6.6 Hz, 2H), 3.21-3.12 (m,




2H), 3.07 (d, J = 9.4 Hz, 2H), 2.03-1.83 (m,




2H)


19
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.30 (s, 1H), 8.29 (d, J = 1.6 Hz,
m/e



ylcarbamoyl)amino]-
1H), 8.02-7.92 (m, 3H), 7.87 (d, J = 9.6 Hz,
372 (M + H)+



N-
1H), 7.79-7.66 (m, 3H),



phenylbenzamide
7.65-7.58 (m, 2H), 7.42-7.33 (m, 2H), 7.20-7.05 (m,




1H)


20
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.39-9.29 (m, 1H),
m/e



ylcarbamoyl)amino]-
8.43-8.29 (m, 1H), 8.09-8.03 (m, 1H),
366 (M + H)+



N-(2-
7.96-7.89 (m, 1H), 7.87-7.75 (m, 3H), 7.66-7.50 (m,



methylbutyl)benzamide
2H), 3.25-3.16 (m, 1H), 3.14-3.03 (m, 1H),




1.70-1.58 (m, 1H), 1.48-1.36 (m, 1H),




1.23-1.05 (m, 1H), 0.97-0.79 (m, 6H)


21
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.44-9.30 (m, 1H),
m/e



ylcarbamoyl)amino]-
8.34 (t, J = 5.8 Hz, 1H), 8.13-8.05 (m, 1H), 7.92 (d,
421 (M + H)+



N-[3-(2-
J = 9.7 Hz, 1H), 7.87-7.76 (m, 3H),



oxopyrrolidin-1-
7.68-7.51 (m, 2H), 3.45-3.32 (m, 2H),



yl)propyl]benzamide
3.31-3.14 (m, 4H), 2.33-2.19 (m, 2H), 2.02-1.87 (m,




2H), 1.80-1.63 (m, 2H)


22
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.34 (d, J = 1.2 Hz, 1H),
m/e



ylcarbamoyl)amino]-
8.33 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz,
394 (M + H)+



N-(tetrahydro-
1H), 7.91 (d, J = 9.6 Hz, 1H), 7.85-7.75 (m,



2H-pyran-4-
3H), 7.62-7.53 (m, 2H), 3.85 (dd, J = 11.4, 2.5 Hz,



ylmethyl)benzamide
2H), 3.27 (td, J = 11.7, 1.9 Hz, 2H), 3.16 (d,




J = 6.9 Hz, 2H), 1.80 (tt, J = 11.3, 3.9 Hz, 1H),




1.59 (d, J = 11.0 Hz, 2H), 1.20 (qd, J = 12.0, 4.5 Hz,




2H)


23
4-[(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-
Temp = 90° C.) δ ppm 9.43-9.28 (m, 1H),
m/e



ylcarbamoyl)amino]-
8.34 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H),
394 (M + H)+



N-(tetrahydro-
7.92 (d, J = 9.7 Hz, 1H), 7.87-7.74 (m, 3H),



2H-pyran-2-
7.65-7.51 (m, 2H), 3.87 (dd, J = 10.6, 2.6 Hz,



ylmethyl)benzamide
1H), 3.48-3.41 (m, 1H), 3.33 (td, J = 11.1, 3.3 Hz,




1H), 3.29-3.21 (m, 2H), 1.78 (d, J = 5.1 Hz,




1H), 1.61 (d, J = 12.8 Hz, 1H),




1.54-1.38 (m, 3H), 1.18 (qd, J = 12.1, 3.7 Hz, 1H)


24
N-[(1,1-

(ESI(+))



dioxidotetrahydrothiophen-

m/e



3-

428 (M + H)+



yl)methyl]-4-



[(imidazo[1,2-



a]pyridin-6-



ylcarbamoyl)amino]benzamide









Example 25
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminophenyl)-5,6-dihydropyridine-1(2H)-carboxylate for 4-amino-N-isopentylbenzamide. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.96 (m, 1H), 8.82-8.75 (m, 1H), 8.65 (m, 1H), 7.96 (s, 1H), 7.52-7.36 (m, 6H), 7.12-7.04 (m, 1H), 6.12-6.05 (m, 1H), 4.07-3.92 (m, 2H), 3.59-3.49 (m, 2H), 2.44 (m, 2H), 1.43 (s, 9H); MS (ESI(+)) m/e 434 (M+H)+.


Example 28
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro furan-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea
Example 28A
1-(imidazo[1,2-a]pyridin-6-yl)-3-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)urea

A solution of tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.57 g, 1.315 mmol) in dichloromethane (5 ml) was treated with trifluoroacetic acid (0.608 ml, 7.88 mmol) and the reaction mixture was stirred at room temperature for 4 hours. Concentration provided the title compound.


Example 28B
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro furan-3-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}urea

The title compound was prepared as described in Example 1A, substituting 1-(imidazo[1,2-a]pyridin-6-yl)-3-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)urea for 3-methylbutan-1-amine and 2-(tetrahydrofuran-3-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.96 (m, 1H), 8.82 (bs, 1H), 8.70 (bs, 1H), 7.96 (s, 1H), 7.55-7.35 (m, 6H), 7.08 (dd, J=9.6, 2.0 Hz, 1H), 6.11 (m, 1H), 4.18-4.05 (m, 2H), 3.90-3.79 (m, 1H), 3.76-3.57 (m, 4H), 3.35-3.23 (m, 2H), 2.55-2.39 (m, 4H), 2.05-1.95 (m, 1H), 1.60-1.42 (m, 1H); MS (ESI(+)) m/e 446 (M+H)+.


Table 3.


The following Examples were prepared essentially as described in Example 28, substituting the appropriate carboxylic acid in Example 28B. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.















Ex
Name

1H NMR

MS







29
1-{4-[1-(2-hydroxy-

1H NMR (300 MHz, DMSO-d6,) δ ppm

(ESI(+))



2-
9.01-8.93 (m, 1H), 8.84 (bs, 1H), 8.71 (bs, 1H),
m/e



methylpropanoyl)-
7.95 (s, 1H), 7.53-7.35 (m, 6H),
420 (M + H)+



1,2,3,6-
7.12-7.04 (m, 1H), 6.13 (m, 1H), 5.43 (bs, 1H),



tetrahydropyridin-4-
4.20-3.95 (m, 2H), 3.31 (m, 2H), 2.58-2.45 (m,



yl]phenyl}-3-
2H), 1.34 (s, 6H)



imidazo[1,2-



a]pyridin-6-ylurea


30
1-imidazo[1,2-

1H NMR (300 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-yl-3-{4-
9.01-8.81 (m, 1H), 7.82 (bs, 1H), 7.54-7.49 (m,
m/e



[1-(morpholin-4-
2H), 7.48-7.32 (m, 4H), 7.18 (dd, J = 9.6,
461 (M + H)+



ylacetyl)-1,2,3,6-
2.0 Hz, 1H), 6.09 (m, 1H), 4.31 (d, J = 2.8 Hz,



tetrahydropyridin-4-
1H), 4.18 (d, J = 2.9 Hz, 1H), 3.89-3.76 (m,



yl]phenyl}urea
2H), 3.71 (m, 4H), 3.38-3.25 (m, 2H),




2.65 (m, 1H), 2.61-2.49 (m, 5H)


31
1-{4-[1-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



(ethoxyacetyl)-
8.85 (d, J = 1.9 Hz, 1H), 8.56 (s, 1H), 8.43 (s, 1H),
m/e



1,2,3,6-
7.87 (s, 1H), 7.50-7.40 (m, 4H),
420 (M + H)+



tetrahydropyridin-4-
7.38-7.32 (m, 2H), 7.10 (dd, J = 9.4, 2.0 Hz, 1H),



yl]phenyl}-3-
6.09-6.04 (m, 1H), 4.13 (s, 2H), 4.13-4.08 (m,



imidazo[1,2-
2H), 3.66 (t, J = 5.7 Hz, 2H), 3.51 (q, J = 6.9 Hz,



a]pyridin-6-ylurea
2H), 2.50-2.45 (m, 2H), 1.14 (t, J = 6.9 Hz,




3H)


32
1-imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-6-yl-3-(4-
8.96 (d, J = 1.9 Hz, 1H), 8.83 (s, 1H), 8.70 (s, 1H),
m/e



{1-[(2-
7.96 (s, 1H), 7.55-7.42 (m, 4H),
450 (M + H)+



methoxyethoxy)acetyl]-
7.42-7.34 (m, 2H), 7.08 (dd, J = 9.6, 2.0 Hz, 1H),



1,2,3,6-
6.15-6.05 (m, 1H), 4.24-4.17 (m, 2H),



tetrahydropyridin-4-
4.12-4.05 (m, 2H), 3.70-3.54 (m, 4H), 3.51-3.43 (m,



yl}phenyl)urea
2H), 3.25 (s, 3H), 2.57-2.41 (m, 2H)


33
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6, Temp = 90° C.)

(ESI(+))



a]pyridin-6-yl-3-{4-
δ ppm 8.89-8.84 (m, 1H), 8.59 (s, 1H),
m/e



[1-(tetrahydrofuran-
8.47 (s, 1H), 7.86 (s, 1H), 7.51-7.40 (m, 4H),
432 (M + H)+



2-ylcarbonyl)-
7.39-7.31 (m, 2H), 7.12-7.08 (m, 1H),



1,2,3,6-
6.10-6.04 (m, 1H), 4.71-4.64 (m, 1H), 4.15 (m,



tetrahydropyridin-4-
2H), 3.84-3.68 (m, 4H), 2.54-2.44 (m, 2H),



yl]phenyl}urea
2.15-1.96 (m, 2H), 1.92-1.81 (m, 2H)


34
1-imidazo[1,2-

1H NMR (300 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-yl-3-{4-
8.93 (dd, J = 2.0, 1.0 Hz, 1H), 7.82 (s, 1H),
m/e



[1-(tetrahydro-2H-
7.56-7.47 (m, 2H), 7.47-7.35 (m, 4H),
446 (M + H)+



pyran-4-
7.22-7.14 (m, 1H), 6.13-6.07 (m, 1H), 4.32-4.16 (m,



ylcarbonyl)-1,2,3,6-
2H), 4.03-3.92 (m, 2H), 3.86-3.77 (m, 2H),



tetrahydropyridin-4-
3.61-3.46 (m, 2H), 3.12-2.92 (m, 1H),



yl]phenyl}urea
2.66-2.49 (m, 2H), 1.92-1.71 (m, 2H),




1.72-1.59 (m, 2H)


35
1-{4-[1-(1,4-dioxan-

1H NMR (400 MHz, DMSO-d6, Temp = 90° C.)

(ESI(+))



2-ylcarbonyl)-
δ ppm 8.86 (d, J = 1.2 Hz, 1H), 8.61 (bs, 1H),
m/e



1,2,3,6-
8.49 (bs, 1H), 7.87 (s, 1H), 7.52-7.40 (m,
448 (M + H)+



tetrahydropyridin-4-
4H), 7.38-7.32 (m, 2H), 7.11 (dd, J = 9.6,



yl]phenyl}-3-
2.0 Hz, 1H), 6.10-6.04 (m, 1H), 4.37 (dd, J = 9.2,



imidazo[1,2-
2.9 Hz, 1H), 4.15 (m, 2H),



a]pyridin-6-ylurea
3.81-3.63 (m, 7H), 3.58-3.45 (m, 1H), 2.56-2.47 (m,




2H)


36
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6, Temp = 90° C.)

(ESI(+))



a]pyridin-6-yl-3-(4-
δ ppm 8.91-8.87 (m 1H), 8.68 (s, 1H),
m/e



{1-[(1-
8.56 (s, 1H), 7.90 (s, 1H), 7.53-7.44 (m, 4H),
459 (M + H)+



methylpiperidin-4-
7.41-7.35 (m, 2H), 7.14 (dd, J = 9.6, 2.1 Hz,



yl)carbonyl]-
1H), 6.14-6.08 (m, 1H), 4.19-4.13 (m, 2H),



1,2,3,6-
3.72 (t, J = 5.7 Hz, 2H), 3.17 (m, 1H),



tetrahydropyridin-4-
2.85-2.77 (m, 2H), 2.64-2.48 (m, 2H), 2.20 (s,



yl}phenyl)urea
3H), 2.06-1.94 (m, 2H), 1.76-1.60 (m, 4H)


37
1-(4-{1-[(1,1-

1H NMR (300 MHz, DMSO-d6) δ

(ESI(+))



dioxidotetrahydro-
8.98-8.94 (m, 1H), 8.83 (bs, 1H), 8.70 (s, 1H),
m/e



2H-thiopyran-4-
7.97-7.94 (m, 1H), 7.55-7.35 (m, 6H), 7.09 (dd, J = 9.6,
494 (M + H)+



yl)carbonyl]-
2.0 Hz, 1H), 6.15-6.09 (m, 1H),



1,2,3,6-
4.27-4.20 (m, 1H), 4.13-4.06 (m, 1H),



tetrahydropyridin-4-
3.79-3.62 (m, 2H), 3.28-3.02 (m, 5H),



yl}phenyl)-3-
2.40-2.60 (m, 2H), 2.08-1.94 (m, 4H)



imidazo[1,2-



a]pyridin-6-ylurea


38
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6, Temp = 90° C.)

(ESI(+))



a]pyridin-6-yl-3-{4-
δ ppm 8.88-8.83 (m, 1H), 8.59 (bs, 1H),
m/e



[1-(2-
8.47 (bs, 1H), 7.87 (s, 1H), 7.50-7.41 (m,
404 (M + H)+



methylpropanoyl)-
4H), 7.39-7.33 (m, 2H), 7.11 (dd, J = 9.5,



1,2,3,6-
2.0 Hz, 1H), 6.12-6.06 (m, 1H),



tetrahydropyridin-4-
4.17-4.11 (m, 2H), 3.69 (t, J = 5.7 Hz, 2H),



yl]phenyl}urea
2.95-2.86 (m, 1H), 2.50 (m, 2H), 1.05 (d, J = 6.7 Hz,




6H)









Example 51
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea
Example 51A
4-(1-isobutyl-1H-pyrazol-4-yl)aniline

A suspension of 4-bromoaniline (406 mg, 2.362 mmol), 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (650 mg, 2.60 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (57.9 mg, 0.071 mmol) and sodium carbonate (526 mg, 4.96 mmol) in a 6:2:1 mixture of tetrahydrofuran/water/methanol (12 ml) in a microwave vial was subjected to three vacuum/nitrogen purge cycles. The vial was sealed and heated in an oil bath at 85° C. overnight. The mixture was dissolved in a mixture of ethyl acetate (45 ml) and water (20 ml), and the separated aqueous layer was extracted with ethyl acetate (20 ml). The combined organic layers were washed with brine (20 ml), dried with magnesium sulfate, filtered and concentrated. Normal phase chromatography provided the title compound.


Example 51B
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea

The title compound was prepared as described in Example 1C, substituting 4-(1-isobutyl-1H-pyrazol-4-yl)aniline for 4-amino-N-isopentylbenzamide. 1H NMR (400 MHz, CDCl3) δ 9.18 (s, 2H), 8.49 (s, 1H), 7.73 (s, 1H), 7.64 (d, J=10.3 Hz, 2H), 7.56 (s, 1H), 7.42-7.31 (m, 4H), 7.36 (d, J=9.5 Hz, 1H), 6.62 (dd, J=9.6, 1.7 Hz, 1H), 3.92 (d, J=7.3 Hz, 2H), 2.23 (hept, J=6.8 Hz, 1H), 0.93 (d, J=6.7 Hz, 6H). MS (ESI)(+)) m/e 375 (M+H)+.


Example 52
4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide
Example 52A
methyl 4-(2-cyclopentylacetamido)benzoate

A solution of methyl 4-aminobenzoate (0.25 g, 1.654 mmol) in tetrahydrofuran (8.27 ml) was treated with diisopropylethylamine (0.433 ml, 2.481 mmol) and 2-cyclopentylacetyl chloride (0.279 g, 1.902 mmol) and the reaction mixture was stirred at ambient temperature for 2 hours. Concentration and normal phase chromatography provided the title compound.


Example 52B
4-(2-cyclopentylacetamido)benzoic acid

The title compound was prepared as described in Example 4B, substituting methyl 4-(2-cyclopentylacetamido)benzoate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 52C
4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.08 (s, 1H), 8.93 (t, J=5.8 Hz, 1H), 8.47 (s, 1H), 7.96 (s, 1H), 7.87-7.81 (m, 2H), 7.70-7.64 (m, 2H), 7.57-7.50 (m, 2H), 7.24 (dd, J=9.2, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 2.36-2.30 (m, 2H), 2.29-2.15 (m, 1H), 1.81-1.65 (m, 2H), 1.67-1.38 (m, 4H), 1.39-0.95 (m, 2H); MS (ESI(+)) m/e 377 (M+H)+.


Example 53
2-[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide
Example 53A
2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-A]pyridin-6-amine (0.768 g, 5.77 mmol) for 3-methylbutan-1-amine and 2-bromo-5-thiazolecarboxylic acid (1 g, 4.81 mmol) for 4-nitrobenzoic acid.


Example 53B
2-(4-cyanobenzylamino)-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide

To a solution of 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide (165 mg, 0.511 mmol) in acetonitrile (2553 μl) was added 4-cyanobenzylamine (67.5 mg, 0.511 mmol). The mixture was heated in a microwave (Biotage Initiator) at 180° C. for 30 minutes. The heating was repeated again after another equivalent of 4-cyanobenzylamine was added. The reaction mixture was purified by normal phase chromatography to provide the title compound.


Example 53C
2-[(4-cyanobenzyl)(3-methylbutanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-yl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 52A, substituting 3-methylbutanoyl chloride for 2-cyclopentylacetyl chloride and 2-(4-cyanobenzylamino)-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H), 9.62 (s, 1H), 8.43 (d, J=1.6 Hz, 1H), 8.32 (s, 1H), 8.11 (s, 1H), 7.99-7.89 (m, 2H), 7.82 (dd, J=18.8, 8.3 Hz, 2H), 7.38 (d, J=8.3 Hz, 2H), 5.63 (s, 2H), 2.14 (dt, J=13.4, 6.7 Hz, 1H), 0.88 (d, J=6.7 Hz, 6H); (APCI(+)) m/e 459 (M+H)+.


Table 4.


The following Examples were prepared essentially as described in Example 53, substituting the appropriate amine in Example 53A, the appropriate amine in 53B and the appropriate acid chloride in Example 53C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.















Ex
Name

1H NMR

MS


















54
2-[(4-

1H NMR (400 MHz, DMSO-d6) δ 10.75 (s,

(APCI(+))



cyanobenzyl)(3-
1H), 9.61 (s, 1H), 8.42 (s, 1H), 8.33 (s, 1H),
m/e



methoxypropanoyl)amino]-
8.10 (s, 1H), 7.94 (s, 2H), 7.84 (d, J = 8.3 Hz,
461 (M + H)+



N-
3H), 7.40 (d, J = 8.3 Hz, 2H), 5.64 (s,



(imidazo[1,2-
2H), 3.64 (t, J = 6.0 Hz, 2H), 3.20 (s, 3H),



a]pyridin-6-yl)-1,3-
2.89 (t, J = 6.1 Hz, 2H).



thiazole-5-



carboxamide


55
2-[(4-

1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H),

(APCI(+))



cyanobenzyl)(3-
8.16 (d, J = 9.5 Hz, 1H), 7.96 (s, 1H),
m/e



methylbutanoyl)amino]-
7.86 (d, J = 1.8 Hz, 1H), 7.81 (d, J = 9.6 Hz,
473 (M + H)+



N-(imidazo[1,2-
1H), 7.75 (s, 1H), 7.63 (d, J = 8.3 Hz, 2H),



a]pyridin-6-
7.24 (d, J = 8.3 Hz, 2H), 5.54 (s, 2H),



ylmethyl)-1,3-
4.69 (d, J = 6.1 Hz, 2H), 2.39 (d, J = 6.7 Hz,



thiazole-5-
2H), 2.30-2.24 (m, 1H), 0.94 (d, J = 6.6 Hz,



carboxamide
6H)


56
2-[(4-

1H NMR (400 MHz, methanol-d4) δ 8.78 (s,

(APCI(+))



cyanobenzyl)(3-
1H), 8.20 (d, J = 2.1 Hz, 1H), 8.02 (d, J = 2.1 Hz,
m/e



methoxypropanoyl)amino]-
1H), 8.01 (s, 1H), 8.00-7.96 (m,
475 (M + H)+



N-
1H), 7.90 (d, J = 9.3 Hz, 1H), 7.70 (d, J = 8.2 Hz,



(imidazo[1,2-
2H), 7.38 (d, J = 8.2 Hz, 2H),



a]pyridin-6-
5.65 (s, 2H), 4.66 (s, 2H), 3.73 (t, J = 5.9 Hz,



ylmethyl)-1,3-
2H), 2.87 (t, J = 5.9 Hz, 2H)



thiazole-5-



carboxamide


57
2-[(4-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



cyanobenzyl)(3-
9.22 (td, J = 6.4, 1.2 Hz, 1H), 8.75 (d, J = 7.0 Hz,
m/e



methoxypropanoyl)amino]-
1H), 8.18 (d, J = 2.0 Hz, 1H),
475 (M + H)+



N-
8.08-7.95 (m, 2H), 7.80 (s, 1H), 7.77-7.66 (m,



(imidazo[1,2-
2H), 7.47 (dd, J = 7.1, 1.1 Hz, 1H), 7.39 (d,



a]pyridin-7-
J = 8.2 Hz, 2H), 5.66 (s, 2H), 4.73 (d, J = 4.5 Hz,



ylmethyl)-1,3-
2H), 3.74 (t, J = 5.9 Hz, 2H),



thiazole-5-
2.88 (t, J = 5.8 Hz, 2H)



carboxamide


61
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.22 (d, J = 2.1 Hz, 1H), 8.08 (s, 1H),
m/e



ylmethyl)-2-[(3-
8.05-7.96 (m, 2H), 7.90 (d, J = 9.3 Hz,
430 (M + H)+



methoxypropanoyl)(3-
1H), 4.67 (d, J = 3.8 Hz, 2H), 4.27 (dd, J = 9.3,



methylbutyl)amino]-
7.0 Hz, 2H), 3.79 (t, J = 5.9 Hz, 2H),



1,3-thiazole-5-
3.36 (s, 3H), 2.98 (t, J = 5.9 Hz, 2H),



carboxamide
1.80-1.67 (m, 1H), 1.67-1.57 (m, 2H), 1.01 (d,




J = 6.5 Hz, 6H)


121
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ 9.11 (t, J = 5.9 Hz,

(APCI(+))



a]pyridin-7-
1H), 8.50 (d, J = 7.0 Hz, 1H),
m/e



ylmethyl)-2-[(3-
8.17 (s, 1H), 7.90 (s, 1H), 7.53 (s, 1H),
444 (M + H)+



methoxypropanoyl)(tetrahydrofuran-
7.41 (s, 1H), 6.85 (dd, J = 7.1, 1.5 Hz, 1H),



2-
4.48 (d, J = 5.8 Hz, 2H), 4.39 (d, J = 12.5 Hz,



ylmethyl)amino]-
1H), 4.25-4.08 (m, 2H), 3.78 (dd, J = 14.8,



1,3-thiazole-5-
6.8 Hz, 1H), 3.66 (t, J = 6.4 Hz, 2H),



carboxamide
3.65-3.55 (m, 1H), 3.26 (s, 3H), 3.06 (ddd, J = 17.2,




13.9, 6.4 Hz, 2H), 1.99 (dd, J = 12.7,




7.4 Hz, 1H), 1.94-1.86 (m, 1H),




1.86-1.74 (m, 1H), 1.66-1.53 (m, 1H)


123
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O) δ ppm

(ESI(+))



a]pyridin-6-
8.76 (s, 1 H) 8.24 (d, J = 2.14 Hz, 1 H)
m/e



ylmethyl)-2-{[(2-
8.10 (s, 1 H) 8.02 (d, J = 2.14 Hz, 1 H) 7.89 (d,
496 (M + H)+



methyl-1,3-thiazol-
J = 1.22 Hz, 2 H) 7.45 (s, 1 H) 4.57 (s, 2 H)



5-
4.50 (d, J = 12.21 Hz, 1 H) 4.42 (d, J = 5.80 Hz,



yl)acetyl](tetrahydrofuran-
1 H) 4.19-4.31 (m, 2 H)



2-
3.78-3.85 (m, 1 H) 3.63-3.69 (m, 1 H)



ylmethyl)amino}-
3.28-3.29 (m, 2 H) 2.62 (s, 3 H) 2.01 (s, 1 H)



1,3-thiazole-5-
1.81-1.95 (m, 2 H) 1.60-1.68 (m, 1 H)



carboxamide


124
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O) δ ppm

(ESI(+))



a]pyridin-6-
8.78 (s, 1 H) 8.26 (d, J = 1.83 Hz, 1 H)
m/e



ylmethyl)-2-{[(2-
8.10 (s, 1 H) 8.05 (d, J = 2.14 Hz, 1 H)
496 (M + H)+



methyl-1,3-thiazol-
7.90-7.96 (m, 2 H) 7.24 (s, 1 H) 4.58 (s, 2 H) 4.47 (dd,



4-
1 H) 4.18-4.37 (m, 4 H) 3.79-3.86 (m, 1



yl)acetyl](tetrahydrofuran-
H) 3.62-3.69 (m, 1 H) 2.62 (s, 3 H)



2-
1.97-2.06 (m, 1 H) 1.80-1.94 (m, 2 H)



ylmethyl)amino}-
1.56-1.69 (m, 1 H)



1,3-thiazole-5-



carboxamide


125
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O) δ ppm

(ESI(+))



a]pyridin-6-
8.70 (s, 1 H) 8.17 (d, J = 1.83 Hz, 1 H)
m/e



ylmethyl)-2-{[(3-
8.10 (s, 1 H) 7.92 (d, J = 1.83 Hz, 1 H)
480 (M + H)+



methyl-1,2-oxazol-
7.79-7.84 (m, 1 H) 7.73-7.85 (m, 1 H) 6.27 (s, 1 H)



5-
4.55 (s, 2 H) 4.35-4.52 (m, 3 H



yl)acetyl](tetrahydrofuran-
4.19-4.27 (m, 2 H) 3.77-3.85 (m, 1 H)



2-
3.62-3.69 (m, 1 H) 2.23 (s, 3 H) 2.01 (d, J = 2.75 Hz,



ylmethyl)amino}-
1 H) 1.80-1.95 (m, 2 H)



1,3-thiazole-5-
1.56-1.67 (m, 1 H)



carboxamide


126
2-{[3-(3-chloro-1,2-

(ESI(+))



oxazol-5-

m/e



yl)propanoyl](tetrahydrofuran-

515 (M + H)+



2-



ylmethyl)amino}-N-



(imidazo[1,2-



a]pyridin-6-



ylmethyl)-1,3-



thiazole-5-



carboxamide


127
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[3-(3-

510 (M + H)+



methoxy-1,2-



oxazol-5-



yl)propanoyl](tetrahydrofuran-



2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


128
2-{[(3,5-dimethyl-

(ESI(+))



1,2-oxazol-4-

m/e



yl)acetyl](tetrahydrofuran-

495 (M + H)+



2-



ylmethyl)amino}-N-



(imidazo[1,2-



a]pyridin-6-



ylmethyl)-1,3-



thiazole-5-



carboxamide


129
2-{[3-(3,5-dimethyl-

(ESI(+))



1,2-oxazol-4-

m/e



yl)propanoyl](tetrahydrofuran-

509 (M + H)+



2-



ylmethyl)amino}-N-



(imidazo[1,2-



a]pyridin-6-



ylmethyl)-1,3-



thiazole-5-



carboxamide


130
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[3-(1-

494 (M + H)+



methyl-1H-pyrazol-



4-



yl)propanoyl](tetrahydrofuran-



2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


131
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[3-(4-

511 (M + H)+



methyl-1,3-thiazol-



5-



yl)propanoyl](tetrahydrofuran-2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


132
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-

468 (M + H)+



[(tetrahydrofuran-2-



ylmethyl)(1H-



tetrazol-5-



ylacetyl)amino]-1,3-



thiazole-5-



carboxamide


133
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[3-

481 (M + H)+



(1,2-oxazol-5-



yl)propanoyl](tetrahydrofuran-



2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


134
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-[(1,2-

467 (M + H)+



oxazol-3-



ylacetyl)(tetrahydrofuran-



2-



ylmethyl)amino]-



1,3-thiazole-5-



carboxamide


135
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[3-

481 (M + H)+



(1,2-oxazol-4-



yl)propanoyl](tetrahydrofuran-



2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


136
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-

497 (M + H)+



{(tetrahydrofuran-2-



ylmethyl)[3-(1,3-



thiazol-2-



yl)propanoyl]amino}-



1,3-thiazole-5-



carboxamide


139
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.22 (d, J = 2.1 Hz, 1H), 8.08 (s, 1H),
m/e



ylmethyl)-2-[(3-
8.03 (d, J = 2.2 Hz, 1H), 7.98 (d, J = 1.4 Hz,
444 (M + H)+



methoxypropanoyl)(tetrahydrofuran-
1H), 7.91 (d, J = 9.3 Hz, 1H), 4.66 (s, 2H),



3-
4.31 (qd, J = 14.8, 7.7 Hz, 2H), 3.96 (td, J = 8.2,



ylmethyl)amino]-
5.7 Hz, 1H), 3.87-3.71 (m, 3H),



1,3-thiazole-5-
3.65 (qd, J = 8.9, 5.6 Hz, 2H), 3.36 (s, 3H),



carboxamide
3.02 (dd, J = 10.4, 5.6 Hz, 2H), 2.94-2.81 (m,




1H), 2.05 (dtd, J = 13.5, 8.0, 5.7 Hz, 1H),




1.75 (ddd, J = 12.6, 7.9, 6.5 Hz, 1H)


140
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 1.9 Hz, 1H), 8.09 (s, 1H),
m/e



ylmethyl)-2-
8.03 (d, J = 2.0 Hz, 1H), 8.00 (d, J = 9.3 Hz,
470 (M + H)+



[(tetrahydrofuran-3-
1H), 7.91 (d, J = 9.2 Hz, 1H), 4.66 (s, 2H),



ylmethyl)(tetrahydro-
4.40 (dd, J = 14.8, 7.0 Hz, 1H), 4.28 (dd, J = 14.7,



2H-pyran-4-
8.5 Hz, 1H), 4.06-3.94 (m, 3H),



ylcarbonyl)amino]-
3.77 (dd, J = 15.0, 8.1 Hz, 1H), 3.68 (dd, J = 8.9,



1,3-thiazole-5-
6.3 Hz, 1H), 3.60 (dd, J = 8.9, 4.7 Hz,



carboxamide
1H), 3.55 (t, J = 11.7 Hz, 2H), 3.24 (tt, J = 11.1,




3.7 Hz, 1H), 2.85 (dt, J = 12.1, 3.5 Hz,




1H), 2.11-2.01 (m, 1H), 1.93 (ddd, J = 16.1,




12.7, 4.3 Hz, 1H), 1.89-1.82 (m,




1H), 1.75 (dt, J = 13.0, 9.9 Hz, 3H)


142
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.22 (d, J = 2.1 Hz, 1H), 8.08 (s, 1H),
m/e



ylmethyl)-2-[(3-
8.03 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 9.4,
458 (M + H)+



methoxypropanoyl)(tetrahydro-
1.4 Hz, 1H), 7.91 (d, J = 9.4 Hz, 1H),



2H-
4.66 (s, 2H), 4.23 (d, J = 7.3 Hz, 2H),



pyran-4-
4.00-3.85 (m, 2H), 3.79 (t, J = 5.9 Hz, 2H),



ylmethyl)amino]-
3.36 (s, 3H), 3.02 (t, J = 5.9 Hz, 2H),



1,3-thiazole-5-
2.26-2.13 (m, 1H), 1.58-1.50 (m, 2H),



carboxamide
1.49-1.36 (m, 2H)


143
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 2.1 Hz, 1H), 8.09 (s, 1H),
m/e



ylmethyl)-2-
8.03 (d, J = 2.0 Hz, 1H), 8.00 (d, J = 9.3 Hz,
470 (M + H)+



[(tetrahydrofuran-3-
1H), 7.91 (d, J = 9.3 Hz, 1H), 4.67 (s, 2H),



ylcarbonyl)(tetrahydro-
4.32-4.23 (m, 2H), 4.08 (t, J = 8.1 Hz,



2H-pyran-4-
1H), 3.94 (qd, J = 9.9, 3.8 Hz, 4H),



ylmethyl)amino]-
3.87 (dd, J = 14.8, 7.3 Hz, 1H), 3.83-3.74 (m,



1,3-thiazole-5-
1H), 3.35 (dd, J = 11.7, 1.9 Hz, 2H),



carboxamide
2.31 (dt, J = 15.4, 7.1 Hz, 1H), 2.18 (td, J = 12.9,




6.6 Hz, 2H), 1.53 (t, J = 10.9 Hz, 2H),




1.50-1.41 (m, 2H)


144
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 2.0 Hz, 1H), 8.09 (s, 1H),
m/e



ylmethyl)-2-
8.03 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 9.3,
484 (M + H)+



[(tetrahydro-2H-
1.4 Hz, 1H), 7.91 (d, J = 9.3 Hz, 1H),



pyran-4-
4.66 (s, 2H), 4.27 (d, J = 7.3 Hz, 2H),



ylcarbonyl)(tetrahydro-
4.03-3.97 (m, 2H), 3.93 (dd, J = 11.4, 2.7 Hz,



2H-pyran-4-
2H), 3.62-3.52 (m, 2H), 3.35 (dd, J = 11.6,



ylmethyl)amino]-
2.2 Hz, 2H), 3.26 (dd, J = 9.3, 5.6 Hz, 1H),



1,3-thiazole-5-
2.21-2.10 (m, 1H), 1.89 (ddd, J = 16.0,



carboxamide
12.6, 4.4 Hz, 2H), 1.76 (dd, J = 13.0, 1.5 Hz,




2H), 1.54 (dt, J = 7.1, 3.0 Hz, 2H),




1.51-1.42 (m, 2H)


145
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.78 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (s, 1H), 8.07 (s, 1H), 8.02 (s, 1H),
m/e



ylmethyl)-2-{(3-
8.00 (d, J = 9.4 Hz, 1H), 7.91 (d, J = 9.4 Hz,
444 (M + H)+



methoxypropanoyl)[(2R)-
1H), 4.66 (s, 2H), 4.52 (d, J = 14.9 Hz, 1H),



tetrahydrofuran-2-
4.29 (d, J = 6.8 Hz, 1H), 4.17 (dd, J = 14.9,



ylmethyl]amino}-
8.9 Hz, 1H), 3.88 (dd, J = 14.5, 7.2 Hz, 1H),



1,3-thiazole-5-
3.76 (dd, J = 14.0, 7.9 Hz, 2H),



carboxamide
3.74-3.69 (m, 1H), 3.36 (s, 3H), 3.13 (q, J = 6.1 Hz,




2H), 2.10 (td, J = 12.4, 7.4 Hz, 1H),




2.04-1.94 (m, 1H), 1.94-1.85 (m, 1H), 1.67 (dq,




J = 15.3, 7.8 Hz, 1H)


146
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (s, 1H), 8.08 (s, 1H), 8.02 (d, J = 1.8 Hz,
m/e



ylmethyl)-2-
1H), 8.00 (d, J = 9.4 Hz, 1H),
456 (M + H)+



{(tetrahydrofuran-3-
7.91 (d, J = 9.3 Hz, 1H), 4.66 (s, 2H), 4.61 (t, J = 13.7 Hz,



ylcarbonyl)[(2R)-
1H), 4.30-4.17 (m, 2H),



tetrahydrofuran-2-
4.06 (ddd, J = 15.8, 14.9, 7.9 Hz, 1H),



ylmethyl]amino}-
3.99-3.91 (m, 2H), 3.90-3.79 (m, 3H),



1,3-thiazole-5-
3.76-3.68 (m, 1H), 2.32 (qd, J = 12.8, 6.7 Hz,



carboxamide
1H), 2.25-2.04 (m, 2H), 2.03-1.86 (m,




2H), 1.72-1.61 (m, 1H)


147
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 2.1 Hz, 1H), 8.07 (s, 1H),
m/e



ylmethyl)-2-{[(2R)-
8.02 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 9.3,
470 (M + H)+



tetrahydrofuran-2-
1.2 Hz, 1H), 7.91 (d, J = 9.3 Hz, 1H),



ylmethyl](tetrahydro-
4.66 (s, 2H), 4.61 (d, J = 12.8 Hz, 1H),



2H-pyran-4-
4.29-4.19 (m, 2H), 4.06-3.96 (m, 2H), 3.85 (dd,



ylcarbonyl)amino}-
J = 14.9, 6.9 Hz, 1H), 3.73 (dd, J = 13.9, 7.7 Hz,



1,3-thiazole-5-
1H), 3.57-3.47 (m, 2H), 3.43 (ddd, J = 14.8,



carboxamide
8.4, 3.9 Hz, 1H), 2.11 (dt, J = 12.1,




5.4 Hz, 1H), 2.05-1.87 (m, 3H),




1.83-1.73 (m, 3H), 1.73-1.64 (m, 1H)


148
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.78 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 1.8 Hz, 1H), 8.06 (s, 1H),
m/e



ylmethyl)-2-{(3-
8.02 (d, J = 2.2 Hz, 1H), 8.00 (dd, J = 9.4,
444 (M + H)+



methoxypropanoyl)[(2S)-
1.5 Hz, 1H), 7.90 (d, J = 9.3 Hz, 1H),



tetrahydrofuran-2-
4.66 (s, 2H), 4.52 (dd, J = 14.9, 2.5 Hz, 1H),



ylmethyl]amino}-
4.32-4.25 (m, 1H), 4.17 (dd, J = 14.8, 8.9 Hz,



1,3-thiazole-5-
1H), 3.92-3.83 (m, 1H),



carboxamide
3.81-3.74 (m, 2H), 3.71 (td, J = 7.7, 6.3 Hz, 1H),




3.36 (s, 3H), 3.21-3.05 (m, 2H), 2.15-2.05 (m,




1H), 2.04-1.95 (m, 1H), 1.91 (ddt, J = 7.5,




5.0, 1.9 Hz, 1H), 1.73-1.60 (m, 1H)


149
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 2.2 Hz, 1H), 8.08 (d, J = 0.7 Hz,
m/e



ylmethyl)-2-
1H), 8.02 (d, J = 2.1 Hz, 1H),
456 (M + H)+



{(tetrahydrofuran-3-
8.00 (dd, J = 9.3, 1.3 Hz, 1H), 7.91 (d, J = 9.3 Hz,



ylcarbonyl)[(2S)-
1H), 4.66 (s, 2H), 4.61 (t, J = 13.2 Hz,



tetrahydrofuran-2-
1H), 4.31-4.17 (m, 2H), 4.06 (ddd, J = 14.8,



ylmethyl]amino}-
14.3, 7.3 Hz, 1H), 4.00-3.92 (m,



1,3-thiazole-5-
2H), 3.90-3.79 (m, 3H), 3.71 (ddd, J = 10.8,



carboxamide
8.3, 3.1 Hz, 1H), 2.39-2.27 (m, 1H),




2.25-2.04 (m, 2H), 2.03-1.87 (m, 2H),




1.73-1.60 (m, 1H)


150
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ 8.79 (s,

(APCI(+))



a]pyridin-6-
1H), 8.21 (d, J = 1.9 Hz, 1H), 8.07 (d, J = 3.1 Hz,
m/e



ylmethyl)-2-{[(2S)-
1H), 8.02 (d, J = 2.2 Hz, 1H),
470 (M + H)+



tetrahydrofuran-2-
8.00 (dd, J = 9.4, 1.5 Hz, 1H), 7.91 (d, J = 9.3 Hz,



ylmethyl](tetrahydro-
1H), 4.66 (s, 2H), 4.61 (d, J = 12.7 Hz,



2H-pyran-4-
1H), 4.31-4.19 (m, 2H), 4.07-3.95 (m,



ylcarbonyl)amino}-
2H), 3.89-3.81 (m, 1H), 3.73 (td, J = 7.8,



1,3-thiazole-5-
6.1 Hz, 1H), 3.58-3.47 (m, 2H),



carboxamide
3.47-3.39 (m, 1H), 2.16-2.05 (m, 1H),




2.05-1.86 (m, 3H), 1.77 (ddd, J = 14.6, 6.0, 2.5 Hz,




3H), 1.73-1.65 (m, 1H)


183
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[(1-

480 (M + H)+



methyl-1H-pyrazol-



4-



yl)acetyl](tetrahydrofuran-



2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


184
2-{[(1,3-dimethyl-

(ESI(+))



1H-pyrazol-4-

m/e



yl)acetyl](tetrahydrofuran-

494 (M + H)+



2-



ylmethyl)amino}-N-



(imidazo[1,2-



a]pyridin-6-



ylmethyl)-1,3-



thiazole-5-



carboxamide


189
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-{[3-(1-

493 (M + H)+



methyl-1H-pyrrol-2-



yl)propanoyl](tetrahydrofuran-



2-



ylmethyl)amino}-



1,3-thiazole-5-



carboxamide


190
2-{[(1,5-dimethyl-

(ESI(+))



1H-pyrazol-3-

m/e



yl)acetyl](tetrahydrofuran-

494 (M + H)+



2-



ylmethyl)amino}-N-



(imidazo[1,2-



a]pyridin-6-



ylmethyl)-1,3-



thiazole-5-



carboxamide


191
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-2-

483 (M + H)+



[(tetrahydrofuran-2-



ylmethyl)(1,3-



thiazol-4-



ylacetyl)amino]-1,3-



thiazole-5-



carboxamide


192
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.73 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 8.64 (d, J = 1.5 Hz, 1H),
m/e



ylmethyl)-2-{(1,2-
8.16 (d, J = 2.1 Hz, 1H), 8.12 (s, 1H),
467 (M + H)+



oxazol-3-
7.98 (d, J = 2.2 Hz, 1H), 7.80 (s, 1H), 7.46 (dd, J = 7.0,



ylacetyl)[(2R)-
1.4 Hz, 1H), 6.52 (d, J = 1.6 Hz, 1H),



tetrahydrofuran-2-
4.72 (s, 2H), 4.65 (dd, J = 14.9, 1.9 Hz,



ylmethyl]amino}-
1H), 4.42 (d, J = 1.4 Hz, 2H), 4.32 (dd, J = 11.6,



1,3-thiazole-5-
4.4 Hz, 1H), 4.23 (dd, J = 14.8, 9.0 Hz,



carboxamide
1H), 3.94 (dd, J = 14.9, 6.8 Hz, 1H),




3.76 (dd, J = 14.2, 7.7 Hz, 1H),




2.21-2.07 (m, 1H), 2.08-1.87 (m, 2H), 1.69 (ddd, J = 15.8,




12.3, 7.6 Hz, 1H)


193
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.74 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 8.17 (d, J = 1.9 Hz, 1H),
m/e



ylmethyl)-2-{[(5-
8.11 (s, 1H), 7.99 (d, J = 2.1 Hz, 1H),
481 (M + H)+



methyl-1,2-oxazol-
7.79 (s, 1H), 7.47 (d, J = 6.8 Hz, 1H), 6.16 (s,



3-yl)acetyl][(2R)-
1H), 4.72 (s, 2H), 4.63 (d, J = 12.8 Hz, 1H),



tetrahydrofuran-2-
4.36-4.27 (m, 3H), 4.21 (dd, J = 14.6, 9.4 Hz,



ylmethyl]amino}-
1H), 3.94 (dd, J = 15.1, 6.8 Hz, 1H),



1,3-thiazole-5-
3.75 (dd, J = 14.3, 7.5 Hz, 1H), 2.43 (s,



carboxamide
3H), 2.13 (d, J = 8.1 Hz, 1H),




2.05-1.89 (m, 2H), 1.75-1.62 (m, 1H)


194
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.74 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 8.27 (d, J = 1.6 Hz, 1H),
m/e



ylmethyl)-2-{[3-
8.17 (d, J = 2.1 Hz, 1H), 8.10 (s, 1H),
481 (M + H)+



(1,2-oxazol-5-
7.99 (d, J = 2.1 Hz, 1H), 7.79 (s, 1H), 7.47 (d, J = 6.8 Hz,



yl)propanoyl][(2R)-
1H), 6.23 (s, 1H), 4.72 (s, 2H),



tetrahydrofuran-2-
4.55 (d, J = 12.6 Hz, 1H), 4.35-4.23 (m,



ylmethyl]amino}-
1H), 4.15 (dd, J = 14.8, 9.0 Hz, 1H),



1,3-thiazole-5-
3.87 (dd, J = 14.8, 6.9 Hz, 1H), 3.72 (dd, J = 14.0,



carboxamide
7.8 Hz, 1H), 3.46 (dd, J = 12.2, 6.1 Hz,




1H), 3.28-3.18 (m, 3H), 2.10 (dd, J = 12.6,




7.2 Hz, 1H), 1.94 (dd, J = 15.7, 8.4 Hz,




2H), 1.74-1.60 (m, 1H)


195
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.71 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 8.51 (s, 1H), 8.36 (s, 1H),
m/e



ylmethyl)-2-{[3-
8.11 (d, J = 17.0 Hz, 2H), 7.94 (d, J = 2.0 Hz,
481 (M + H)+



(1,2-oxazol-4-
1H), 7.76 (s, 1H), 7.42 (d, J = 6.8 Hz,



yl)propanoyl][(2R)-
1H), 4.71 (s, 2H), 4.53 (d, J = 12.5 Hz, 1H),



tetrahydrofuran-2-
4.27 (t, J = 6.7 Hz, 1H), 4.14 (dd, J = 14.9,



ylmethyl]amino}-
9.1 Hz, 1H), 3.83 (dd, J = 14.9, 6.8 Hz, 1H),



1,3-thiazole-5-
3.69 (dd, J = 13.8, 7.5 Hz, 1H), 3.26 (d, J = 7.1 Hz,



carboxamide
1H), 3.09 (dd, J = 17.6, 6.4 Hz, 1H),




2.91 (dd, J = 12.3, 6.4 Hz, 2H), 2.10 (dt, J = 12.3,




5.9 Hz, 1H), 2.03-1.84 (m, 2H),




1.74-1.58 (m, 1H)


196
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 9.00 (s,

(APCI(+))



a]pyridin-7-
1H), 8.74 (d, J = 7.0 Hz, 1H), 8.17 (d, J = 1.9 Hz,
m/e



ylmethyl)-2-{[(2R)-
1H), 8.11 (s, 1H), 7.98 (d, J = 2.2 Hz,
483 (M + H)+



tetrahydrofuran-2-
1H), 7.79 (s, 1H), 7.51 (s, 1H), 7.47 (d,



ylmethyl](1,3-
J = 7.0 Hz, 1H), 4.72 (s, 2H), 4.63 (d, J = 12.8 Hz,



thiazol-4-
1H), 4.49 (q, J = 16.9 Hz, 2H),



ylacetyl)amino}-
4.38-4.25 (m, 2H), 3.96 (dd, J = 14.9, 6.7 Hz,



1,3-thiazole-5-
1H), 3.76 (dd, J = 14.2, 7.6 Hz, 1H),



carboxamide
2.19-2.08 (m, 1H), 2.06-1.98 (m, 1H),




1.98-1.89 (m, 1H), 1.70 (td, J = 15.6, 7.6 Hz,




1H)


197
2-{[(1,5-dimethyl-

1H NMR (400 MHz, methanol-d4) δ 8.74 (d,

(APCI(+))



1H-pyrazol-3-
J = 7.0 Hz, 1H), 8.17 (d, J = 2.1 Hz, 1H),
m/e



yl)acetyl][(2R)-
8.10 (s, 1H), 7.99 (d, J = 2.1 Hz, 1H),
494 (M + H)+



tetrahydrofuran-2-
7.79 (s, 1H), 7.47 (d, J = 7.0 Hz, 1H), 6.01 (s,



ylmethyl]amino}-N-
1H), 4.72 (s, 2H), 4.55 (d, J = 12.9 Hz, 1H),



(imidazo[1,2-
4.30 (t, J = 7.9 Hz, 1H), 4.27-4.18 (m,



a]pyridin-7-
2H), 4.10 (t, J = 15.1 Hz, 1H), 3.94 (dd, J = 14.8,



ylmethyl)-1,3-
6.8 Hz, 1H), 3.82-3.68 (m, 4H),



thiazole-5-
2.27 (s, 3H), 2.20-2.06 (m, 1H), 2.00 (dd, J = 13.5,



carboxamide
5.8 Hz, 1H), 1.97-1.87 (m, 1H),




1.76-1.58 (m, 1H)


198
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.75 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 8.17 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-{[3-(1-
8.09 (s, 1H), 7.99 (d, J = 2.1 Hz, 1H),
494 (M + H)+



methyl-1H-pyrazol-
7.80 (s, 1H), 7.47 (d, J = 8.2 Hz, 1H), 7.45 (s,



4-
1H), 7.36 (s, 1H), 4.72 (s, 2H), 4.50 (dd, J = 14.9,



yl)propanoyl][(2R)-
2.3 Hz, 1H), 4.27 (t, J = 6.9 Hz, 1H),



tetrahydrofuran-2-
4.13 (dd, J = 14.9, 9.0 Hz, 1H),



ylmethyl]amino}-
3.89-3.76 (m, 4H), 3.70 (dd, J = 14.1, 7.6 Hz, 1H),



1,3-thiazole-5-
3.21 (dt, J = 17.0, 7.2 Hz, 1H), 3.05 (dt, J = 16.9,



carboxamide
6.9 Hz, 1H), 2.88 (t, J = 7.1 Hz, 2H),




2.09 (dt, J = 12.1, 7.6 Hz, 1H), 1.92 (ddd, J = 19.6,




13.4, 7.1 Hz, 2H), 1.65 (dt, J = 19.6,




7.6 Hz, 1H)


199
2-{[(3,5-dimethyl-

1H NMR (400 MHz, methanol-d4) δ 8.74 (d,

(APCI(+))



1,2-oxazol-4-
J = 7.0 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H),
m/e



yl)acetyl][(2R)-
8.11 (s, 1H), 7.99 (d, J = 2.2 Hz, 1H),
495 (M + H)+



tetrahydrofuran-2-
7.79 (s, 1H), 7.47 (d, J = 7.1 Hz, 1H), 4.72 (s,



ylmethyl]amino}-N-
2H), 4.68 (d, J = 13.1 Hz, 1H),



(imidazo[1,2-
4.39-4.19 (m, 3H), 4.03-3.88 (m, 2H), 3.77 (dd, J = 13.8,



a]pyridin-7-
7.6 Hz, 1H), 2.32 (s, 3H),



ylmethyl)-1,3-
2.23-2.11 (m, 4H), 2.09-1.91 (m, 2H),



thiazole-5-
1.77-1.63 (m, 1H)



carboxamide


202
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 9.20 (s,

(APCI(+))



a]pyridin-7-
1H), 8.74 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 2.0 Hz,
m/e



ylmethyl)-2-{[(1-
1H), 8.10 (s, 1H), 7.99 (d, J = 2.1 Hz,
480 (M + H)+



methyl-1H-pyrazol-
1H), 7.79 (s, 1H), 7.57 (s, 1H), 7.47 (d,



4-yl)acetyl][(2R)-
J = 5.9 Hz, 1H), 7.42 (s, 1H), 4.72 (s, 2H),



tetrahydrofuran-2-
4.59 (d, J = 13.1 Hz, 1H), 4.31 (t, J = 7.1 Hz,



ylmethyl]amino}-
1H), 4.22 (dd, J = 14.7, 9.1 Hz, 1H),



1,3-thiazole-5-
4.11 (s, 2H), 3.92 (dd, J = 14.9, 6.9 Hz,



carboxamide
1H), 3.87 (s, 3H), 3.76 (dd, J = 14.2, 7.7 Hz,




1H), 2.19-2.06 (m, 1H), 2.00 (d, J = 7.3 Hz,




1H), 1.94 (dd, J = 13.4, 6.2 Hz, 1H),




1.69 (dt, J = 15.5, 7.5 Hz, 1H)


203
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ 8.74 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H),
m/e



ylmethyl)-2-{[3-(1-
8.10 (s, 1H), 7.99 (d, J = 2.1 Hz, 1H),
493 (M + H)+



methyl-1H-pyrrol-2-
7.80 (s, 1H), 7.47 (d, J = 7.0 Hz, 1H), 6.54 (d, J = 2.5 Hz,



yl)propanoyl][(2R)-
1H), 5.91 (t, J = 3.1 Hz, 1H),



tetrahydrofuran-2-
5.83 (s, 1H), 4.72 (s, 2H), 4.50 (dd, J = 14.9, 2.3 Hz,



ylmethyl]amino}-
1H), 4.28 (t, J = 6.8 Hz, 1H), 4.12 (dd,



1,3-thiazole-5-
J = 14.8, 8.9 Hz, 1H), 3.85 (dd, J = 14.9, 6.8 Hz,



carboxamide
1H), 3.77-3.65 (m, 1H), 3.58 (s, 3H),




3.25 (t, J = 8.4 Hz, 1H), 3.16-3.02 (m,




1H), 2.96 (t, J = 7.4 Hz, 2H), 2.10 (dt, J = 12.0,




7.3 Hz, 1H), 2.04-1.81 (m, 2H),




1.66 (dt, J = 15.7, 7.4 Hz, 1H)









Example 58
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]butyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminobutyl)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide. 1H NMR (500 MHz, DMSO-d6, Temp=90° C.) δ ppm 8.79-8.76 (m, 1H), 8.10 (bs, 1H), 7.81-7.78 (m, 1H), 7.45-7.37 (m, 2H), 7.02 (dd, J=9.5, 2.1 Hz, 1H), 6.04-5.96 (m, 1H), 3.93-3.85 (m, 2H), 3.14-3.06 (m, 2H), 2.75-2.63 (m, 2H), 1.67-1.57 (m, 2H), 1.50-1.19 (m, 16H), 1.07-0.91 (m, 2H); MS (ESI(+)) m/e 416 (M+H)+.


Example 59
4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)benzamide

The title compound was prepared as described in Example 1, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for imidazo[1,2-a]pyridin-6-amine in Example 1C. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.87 (s, 1H), 8.46-8.41 (m, 1H), 8.23-8.15 (m, 1H), 7.97-7.93 (m, 1H), 7.76-7.70 (m, 2H), 7.57-7.51 (m, 2H), 7.49-7.43 (m, 2H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 6.77 (t, J=5.9 Hz, 1H), 4.30 (d, J=5.8 Hz, 2H), 3.29-3.19 (m, 2H), 1.67-1.53 (m, 1H), 1.45-1.35 (m, 2H), 0.93-0.87 (m, 6H); MS (ESI(+)) m/e 380 (M+H)+.


Example 60
2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide

The title compound was prepared as described in Example 3, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for imidazo[1,2-a]pyridin-6-amine in Example 3A. 1H NMR (400 MHz, DMSO-d6, Temp=90° C.) δ 9.34 (bs, 1H), 8.71 (s, 1H), 8.38-8.33 (m, 1H), 8.23 (d, J=1.9 Hz, 1H), 7.97 (d, J=1.9 Hz, 1H), 7.86-7.75 (m, 2H), 7.44-7.38 (m, 2H), 7.32-7.26 (m, 2H), 6.69-6.62 (m, 1H), 4.43-4.38 (m, 2H), 2.29-2.18 (m, 3H), 1.81-1.68 (m, 2H), 1.67-1.45 (m, 4H), 1.29-1.15 (m, 2H); MS (ESI(+)) m/e 392 (M+H)+.


Example 62
1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}butyl)urea
Example 62A
4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]butyl}piperidine

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]butyl}piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 62B
1-imidazo[1,2-a]pyridin-6-yl-3-(4-{1-[(propan-2-yloxy)acetyl]piperidin-4-yl}butyl)urea

The title compound was prepared as described in Example 1A, substituting 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]butyl}piperidine for 3-methylbutan-1-amine and 2-isopropoxyacetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6/D2O) δ ppm 9.18 (dd, J=1.9, 0.8 Hz, 1H), 8.30-8.19 (m, 1H), 7.98 (d, J=2.1 Hz, 1H), 7.84 (d, J=9.7 Hz, 1H), 7.76-7.72 (m, 1H), 4.03 (s, 4H), 3.72-3.52 (m, 1H), 3.14 (t, J=6.9 Hz, 2H), 2.77 (s, 2H), 1.69 (dd, J=12.9, 2.3 Hz, 2H), 1.58-1.40 (m, 4H), 1.41-1.31 (m, 2H), 1.31-1.21 (m, 2H), 1.11 (t, J=5.2 Hz, 6H), 1.03 (d, J=10.2 Hz, 2H); MS (ESI(+)) m/e 416 (M+H)+.


Table 5.


The following Examples were prepared essentially as described in Example 62, substituting the appropriate carboxylic acid in Example 62B. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.















Ex
Name

1H NMR

MS


















63
1-{4-[1-(1,4-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



dioxan-2-
Temp = 90° C.) δ ppm 9.17 (dd, J = 2.0, 0.8 Hz,
m/e



ylcarbonyl)piperidin-
1H), 8.23 (d, J = 1.7 Hz, 1H), 7.97 (d, J = 2.1 Hz,
430 (M + H)+



4-yl]butyl}-3-
1H), 7.83 (d, J = 9.7 Hz, 1H), 7.74 (dd, J = 9.7,



imidazo[1,2-
1.9 Hz, 1H), 4.27 (dt, J = 16.5, 8.3 Hz,



a]pyridin-6-ylurea
1H), 3.80-3.70 (m, 2H), 3.70-3.58 (m, 3H),




3.58-3.43 (m, 1H), 3.13 (q, J = 7.1 Hz, 2H),




1.69 (d, J = 11.6 Hz, 2H), 1.56-1.43 (m, 4H),




1.42-1.21 (m, 6H), 1.03 (s, 2H)


64
1-{4-[1-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



(cyclopropylacetyl)piperidin-
Temp = 90° C.) δ ppm 9.25-9.11 (m, 1H),
m/e



4-
8.24 (d, J = 1.8 Hz, 1H), 7.98 (d, J = 2.0 Hz, 1H),
398 (M + H)+



yl]butyl}-3-
7.84 (d, J = 9.7 Hz, 1H), 7.81-7.71 (m, 1H),



imidazo[1,2-
3.98 (s, 1H), 3.24-3.06 (m, 3H), 2.23 (d, J = 6.7 Hz,



a]pyridin-6-ylurea
2H), 1.68 (d, J = 12.9 Hz, 2H),




1.61-1.41 (m, 4H), 1.39-1.20 (m, 4H),




1.09-0.85 (m, 4H), 0.49-0.35 (m, 2H), 0.22-0.05 (m,




2H)


65
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.24-9.11 (m, 1H),
m/e



{4-[1-(4,4,4-
8.23 (d, J = 2.1 Hz, 1H), 7.97 (d, J = 2.0 Hz, 1H),
440 (M + H)+



trifluorobutanoyl)piperidin-
7.83 (d, J = 9.7 Hz, 1H), 7.77-7.69 (m, 1H),



4-
3.14 (t, J = 6.9 Hz, 2H), 2.56 (dd, J = 10.8, 4.4 Hz,



yl]butyl}urea
3H), 2.51-2.40 (m, 2H), 1.69 (d, J = 12.0 Hz,




2H), 1.63-1.43 (m, 4H), 1.41-1.22 (m,




4H), 0.98 (dd, J = 36.1, 8.5 Hz, 2H)


66
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.17 (dd, J = 1.9, 0.8 Hz,
m/e



{4-[1-(tetrahydro-
1H); 8.23 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 2.1 Hz,
402 (M + H)+



2H-pyran-4-
1H), 7.82 (d, J = 9.3 Hz, 1H), 7.73 (dd, J = 9.7,



ylacetyl)piperidin-
1.9 Hz, 1H), 7.55 (dd, J = 8.4, 4.5 Hz, 2H),



4-yl]butyl}urea
4.46 (d, J = 12.6 Hz, 2H), 3.16 (dd, J = 18.1,




11.2 Hz, 2H), 2.78 (t, J = 12.3 Hz, 3H), 1.68 (d,




J = 9.8 Hz, 2H), 1.54-1.42 (m, 4H), 1.33 (s,




8H), 1.26 (t, J = 7.0 Hz, 3H), 1.11-0.99 (m,




2H)


67
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.17 (dd, J = 1.9, 0.8 Hz,
m/e



{4-[1-
1H), 8.30-8.19 (m, 1H), 7.98 (d, J = 2.1 Hz,
442 (M + H)+



(tetrahydrofuran-2-
1H), 7.83 (d, J = 9.6 Hz, 1H), 7.75 (dd, J = 9.6,



ylacetyl)piperidin-
1.9 Hz, 1H), 3.88-3.71 (m, 2H), 3.14 (t, J = 6.9 Hz,



4-yl]butyl}urea
2H), 2.23 (t, J = 6.9 Hz, 2H), 1.91 (ttd,




J = 10.7, 6.9, 3.5 Hz, 1H), 1.68 (d, J = 12.1 Hz,




2H), 1.56 (t, J = 12.5 Hz, 2H), 1.53-1.42 (m,




4H), 1.42-1.28 (m, 2H), 1.22 (m, 4H),




0.99 (d, J = 10.1 Hz, 2H)


68
1-{4-[1-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



(cyclopentylcarbonyl)piperidin-
Temp = 90° C.) δ ppm 9.23-9.13 (m, 1H),
m/e



4-
8.23 (d, J = 2.1 Hz, 1H), 7.97 (d, J = 2.0 Hz, 1H),
412 (M + H)+



yl]butyl}-3-
7.83 (d, J = 9.7 Hz, 1H), 7.82-7.71 (m, 1H),



imidazo[1,2-
4.12 (s, 2H), 3.98 (s, 1H), 3.14 (t, J = 6.9 Hz,



a]pyridin-6-ylurea
2H), 3.04-2.89 (m, 2H), 2.77 (s, 2H),




1.87-1.59 (m, 8H), 1.51-1.33 (m, 6H),




1.40-1.10 (m, 4H), 1.08-0.91 (m, 2H)


69
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ 9 ppm. 23-9.14 (m, 1H),
m/e



{4-[1-(tetrahydro-
8.24 (d, J = 1.9 Hz, 1H), 7.98 (d, J = 2.1 Hz, 1H),
428 (M + H)+



2H-pyran-4-
7.84 (d, J = 9.7 Hz, 1H), 7.79-7.68 (m, 1H),



ylcarbonyl)piperidin-
4.11 (s, 2H), 3.88-3.77 (m, 2H),



4-yl]butyl}urea
3.51-3.36 (m, 2H), 3.21-3.09 (m, 2H), 2.92-2.73 (m,




2H), 1.76-1.56 (m, 4H), 1.56-1.42 (m, 6H),




1.45-1.18 (m, 4H), 1.04-0.87 (m, 2H)


70
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.17 (dd, J = 1.9, 0.8 Hz,
m/e



(4-{1-[(2-
1H), 8.24 (d, J = 1.9 Hz, 1H), 7.98 (d, J = 2.1 Hz,
432 (M + H)+



methoxyethoxy)acetyl]piperidin-
1H), 7.84 (d, J = 9.7 Hz, 1H), 7.75 (dd, J = 9.7,



4-
1.9 Hz, 1H), 4.09 (d, J = 7.6 Hz, 2H),



yl}butyl)urea
3.56 (dd, J = 6.0, 3.8 Hz, 2H), 3.47 (dd, J = 5.7, 3.7 Hz,




2H), 3.26 (s, 2H), 3.19-3.07 (m, 2H),




1.68 (dd, J = 13.0, 2.2 Hz, 2H), 1.48 (dt, J = 14.1,




7.0 Hz, 4H), 1.40-1.22 (m, 6H), 1.04 (d, J = 9.3 Hz,




2H)


71
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.26-9.11 (m, 1H),
m/e



{4-[1-(morpholin-
8.23 (d, J = 1.8 Hz, 1H), 7.98 (d, J = 2.1 Hz, 1H),
443 (M + H)+



4-
7.83 (t, J = 8.1 Hz, 1H), 7.80-7.71 (m, 1H),



ylacetyl)piperidin-
4.22 (s, 2H), 3.98 (s, 1H), 3.93-3.84 (m, 4H),



4-yl]butyl}urea
3.62 (s, 1H), 3.18-3.07 (m, 2H), 2.71 (s, 2H),




1.80-1.67 (m, 2H), 1.51 (dq, J = 21.7, 7.0 Hz,




4H), 1.42-1.20 (m, 6H), 1.07 (s, 2H)


72
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.25-9.14 (m, 1H),
m/e



{4-[1-
8.24 (d, J = 1.9 Hz, 1H), 7.98 (d, J = 2.0 Hz, 1H),
414 (M + H)+



(tetrahydrofuran-3-
7.84 (d, J = 9.7 Hz, 1H), 7.79-7.69 (m, 1H),



ylcarbonyl)piperidin-
3.85 (t, J = 8.1 Hz, 2H), 3.70 (h, J = 7.8 Hz,



4-yl]butyl}urea
4H), 3.20-3.08 (m, 2H), 2.09-1.91 (m, 2H),




1.70 (d, J = 12.1 Hz, 2H), 1.61-1.43 (m, 4H),




1.37-1.24 (m, 4H), 1.08-0.88 (m, 2H)


73
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.22-9.12 (m, 1H),
m/e



{4-[1-
8.24 (d, J = 2.1 Hz, 1H), 7.98 (d, J = 2.0 Hz, 1H),
428 (M + H)+



(tetrahydrofuran-3-
7.84 (d, J = 9.7 Hz, 1H), 7.79-7.69 (m, 1H),



ylacetyl)piperidin-
3.98 (s, 1H), 3.86-3.76 (m, 1H),



4-yl]butyl}urea
3.75-3.68 (m, 1H), 3.68-3.57 (m, 1H), 3.28-3.23 (m,




1H), 3.14 (t, J = 6.9 Hz, 2H), 2.50-2.43 (m,




1H), 2.43-2.30 (m, 2H), 2.09-1.92 (m, 1H),




1.68 (d, J = 13.3 Hz, 2H), 1.56-1.41 (m, 6H),




1.38-1.29 (m, 2H), 1.25 (dd, J = 14.2, 6.0 Hz,




2H), 1.00 (d, J = 10.2 Hz, 2H)


74
1-imidazo[1,2-

1H NMR (400 MHz, DMSO-d6/D2O,

(ESI(+))



a]pyridin-6-yl-3-
Temp = 90° C.) δ ppm 9.18 (d, J = 1.1 Hz, 1H),
m/e



{4-[1-
8.24 (d, J = 2.0 Hz, 1H), 7.98 (d, J = 2.0 Hz,
414 (M + H)+



(tetrahydrofuran-2-
1H), 7.84 (d, J = 9.6 Hz, 1H), 7.79-7.65 (m,



ylcarbonyl)piperidin-
1H), 4.59 (t, J = 6.7 Hz, 1H), 4.12 (s, 2H),



4-yl]butyl}urea
3.88-3.62 (m, 2H), 3.16 (dd, J = 18.1, 11.3 Hz,




2H), 2.02-1.93 (m, 2H), 1.93-1.72 (m, 2H),




1.69 (d, J = 12.7 Hz, 2H), 1.58-1.43 (m, 4H),




1.42-1.19 (m, 5H), 1.17-0.87 (m, 2H)


107
1-[4-(1-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



benzoylpiperidin-
8.82-8.77 (m, 1H), 7.76 (s, 1H), 7.50 (s, 1H),
m/e



4-yl)butyl]-3-
7.48-7.40 (m, 4H), 7.42-7.33 (m, 2H), 7.09 (dd, J = 9.5,
420 (M + H)+



imidazo[1,2-
2.0 Hz, 1H), 4.65-4.57 (m, 1H),



a]pyridin-6-ylurea
3.74-3.65 (m, 1H), 3.21 (t, J = 6.9 Hz, 2H),




3.13-3.03 (m, 1H), 2.88-2.78 (m, 1H),




1.90-1.82 (m, 1H), 1.74-1.46 (m, 4H), 1.48-1.26 (m,




4H), 1.28-1.04 (m, 2H)


270
1-[4-(1-

(ESI(+))



benzoylpiperidin-

m/e



4-yl)butyl]-3-

420 (M + H)+



imidazo[1,2-



a]pyridin-7-ylurea









Example 75
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide
Example 75A
5-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 5-bromothiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 75B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 5-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.99 (t, J=5.8 Hz, 1H), 8.46 (s, 1H), 8.14 (s, 1H), 7.95 (s, 1H), 7.79 (s, 1H), 7.69 (d, J=3.9 Hz, 1H), 7.49-7.58 (m, 2H), 7.20 (d, J=4.0 Hz, 2H), 4.43 (d, J=5.7 Hz, 2H), 3.91 (d, J=7.2 Hz, 2H), 2.11 (dq, J=13.6, 6.8 Hz, 1H), 0.84 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 380 (M+H)+.


Table 6.


The following Examples were prepared essentially as described in Example 75, substituting the appropriate carboxylic acid and amine in Example 75A and the appropriate boronate in Example 75B. Some boronates were Boc-protected and required deprotection as in Example 28A.















Ex
Name

1H NMR

MS


















120
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-6-
8.87 (t, J = 6.0 Hz, 1 H), 8.46 (s, 1 H), 8.14 (s, 1 H),
m/e



ylmethyl)-5-[1-(2-
7.96 (s, 1 H), 7.87 (s, 1 H), 7.53 (d, J = 6.8 Hz,
364 (M + H)+



methylpropyl)-1H-
2 H), 7.21 (dd, J = 9.3, 1.4 Hz, 1 H), 7.14 (d,



pyrazol-4-yl]furan-
J = 3.6 Hz, 1 H), 6.64 (d, J = 3.5 Hz, 1 H),



2-carboxamide
4.44 (d, J = 6.0 Hz, 2 H), 3.94 (d, J = 7.2 Hz, 2 H),




2.11 (dq, J = 13.6, 6.8 Hz, 1 H), 0.83 (d, J = 6.7 Hz,




6 H)


174
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.04 (t, J = 6.0 Hz, 1 H), 8.48 (d, J = 7.0 Hz, 1 H),
m/e



ylmethyl)-5-[1-(2-
8.14 (s, 1 H), 7.88 (s, 1 H), 7.80 (s, 1 H),
380 (M + H)+



methylpropyl)-1H-
7.73 (d, J = 3.8 Hz, 1 H), 7.51 (s, 1 H), 7.38 (s, 1 H),



pyrazol-4-
7.21 (d, J = 3.9 Hz, 1 H), 6.84 (dd, J = 7.0, 1.5 Hz,



yl]thiophene-2-
1 H), 4.46 (d, J = 5.9 Hz, 2 H), 3.91 (d,



carboxamide
J = 7.3 Hz, 2 H), 2.11 (dq, J = 13.6, 6.7, 6.6 Hz,




1 H), 0.84 (d, J = 6.7 Hz, 6 H)


175
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm




a]pyridin-6-
9.09 (t, J = 5.9 Hz, 1 H), 8.81 (s, 1 H), 8.47 (s, 1 H),



ylmethyl)-5-[1-(2-
8.31 (s, 1 H), 7.95 (s, 1 H), 7.76 (d, J = 3.9 Hz,



methylpropanoyl)-
1 H), 7.54 (t, J = 4.6 Hz, 2 H), 7.50 (d, J = 3.9 Hz,



1H-pyrazol-4-
1 H), 7.20 (dd, J = 9.2, 1.5 Hz, 1 H),



yl]thiophene-2-
4.44 (d, J = 5.9 Hz, 2 H), 3.77 (dq, J = 6.9 Hz, 1 H),



carboxamide
1.21 (d, J = 6.9 Hz, 6 H)


176
5-[1-(2-hydroxy-2-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



methylpropyl)-1H-
9.00 (t, J = 5.9 Hz, 1 H), 8.46 (s, 1 H), 8.03 (s, 1 H),
m/e



pyrazol-4-yl]-N-
7.95 (s, 1 H), 7.78 (s, 1 H), 7.69 (d, J = 3.8 Hz,
396 (M + H)+



(imidazo[1,2-
1 H), 7.49-7.58 (m, 2 H), 7.16-7.25 (m, 2



a]pyridin-6-
H), 4.76 (s, 1 H), 4.42 (d, J = 5.7 Hz, 2 H),



ylmethyl)thiophene-
4.01 (s, 2 H), 1.06 (s, 6 H)



2-carboxamide


177
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm




a]pyridin-6-
9.00 (t, J = 5.9 Hz, 1 H), 8.46 (s, 1 H), 8.19 (s, 1 H),



ylmethyl)-5-{1-[(3-
7.95 (s, 1 H), 7.83 (s, 1 H), 7.70 (d, J = 3.9 Hz,



methyloxetan-3-
1 H), 7.48-7.58 (m, 2 H), 7.15-7.24 (m, 2



yl)methyl]-1H-
H), 4.59 (d, J = 6.0 Hz, 2 H), 4.42 (d, J = 5.9 Hz,



pyrazol-4-
2 H), 4.33 (s, 2 H), 4.22 (d, J = 6.0 Hz, 2 H),



yl}thiophene-2-
1.13 (s, 3 H)



carboxamide


178
5-[1-

1H NMR (400 MHz, DMSO-d6) δ ppm




(cyclobutylmethyl)-
8.99 (t, J = 5.9 Hz, 1 H), 8.46 (s, 1 H), 8.13 (s, 1 H),



1H-pyrazol-4-yl]-
7.95 (s, 1 H), 7.77 (s, 1 H), 7.69 (d, J = 3.9 Hz,



N-(imidazo[1,2-
1 H), 7.48-7.57 (m, 2 H), 7.16-7.23 (m, 2



a]pyridin-6-
H), 4.42 (d, J = 5.7 Hz, 2 H), 4.12 (d, J = 7.3 Hz,



ylmethyl)thiophene-
2 H), 2.74 (dq, J = 7.5, 7.4 Hz, 1 H),



2-carboxamide
1.90-2.02 (m, 2 H), 1.67-1.90 (m, 4 H)


179
5-[1-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



(cyclohexylmethyl)-
8.99 (t, J = 5.9 Hz, 1 H), 8.46 (s, 1 H), 8.12 (s, 1 H),
m/e



1H-pyrazol-4-yl]-
7.95 (s, 1 H), 7.78 (s, 1 H), 7.69 (d, J = 3.9 Hz,
420 (M + H)+



N-(imidazo[1,2-
1 H), 7.48-7.57 (m, 2 H), 7.14-7.26 (m, 2



a]pyridin-6-
H), 4.42 (d, J = 5.9 Hz, 2 H), 3.93 (d, J = 7.2 Hz,



ylmethyl)thiophene-
2 H), 1.72-1.88 (m, 1 H), 1.54-1.70 (m, 3



2-carboxamide
H), 1.50 (d, J = 12.1 Hz, 2 H), 1.03-1.28 (m, 3




H), 0.85-1.01 (m, 2 H)


180
5-{1-[(2R)-2-

1H NMR (400 MHz, DMSO-d6) δ ppm




hydroxybutyl]-1H-
8.99 (t, J = 5.8 Hz, 1 H), 8.46 (s, 1 H), 8.08 (s, 1 H),



pyrazol-4-yl}-N-
7.95 (s, 1 H), 7.78 (s, 1 H), 7.69 (d, J = 3.9 Hz,



(imidazo[1,2-
1 H), 7.50-7.58 (m, 2 H), 7.17-7.23 (m, 2



a]pyridin-6-
H), 4.92 (d, J = 5.4 Hz, 1 H), 4.42 (d, J = 5.7 Hz,



ylmethyl)thiophene-
2 H), 4.03-4.12 (m, 1 H), 3.93-4.02 (m, 1



2-carboxamide
H), 3.66-3.76 (m, 1 H), 1.20-1.44 (m, 2 H),




0.88 (t, J = 7.4 Hz, 3 H)


182
5-[1-(2-hydroxy-2-

1H NMR (400 MHz, DMSO-d6) δ ppm




methylpropyl)-1H-
9.04 (t, J = 5.9 Hz, 1 H), 8.48 (d, J = 7.0 Hz, 1 H),



pyrazol-4-yl]-N-
8.04 (s, 1 H), 7.88 (s, 1 H), 7.79 (s, 1 H),



(imidazo[1,2-
7.73 (d, J = 3.8 Hz, 1 H), 7.51 (s, 1 H), 7.38 (s, 1 H),



a]pyridin-7-
7.23 (d, J = 3.8 Hz, 1 H), 6.84 (dd, J = 7.0, 1.3 Hz,



ylmethyl)thiophene-
1 H), 4.75 (s, 1 H), 4.46 (d, J = 5.9 Hz, 2



2-carboxamide
H), 4.01 (s, 2 H), 1.07 (s, 6 H)


186
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-6-
9.00 (t, J = 5.8 Hz, 1 H), 8.46 (s, 1 H), 8.07 (s, 1 H),
m/e



ylmethyl)-5-[1-
7.95 (s, 1 H), 7.78 (s, 1 H), 7.69 (d, J = 3.8 Hz,
422 (M + H)+



(tetrahydro-2H-
1 H), 7.48-7.57 (m, 2 H), 7.14-7.27 (m, 2



pyran-2-ylmethyl)-
H), 4.42 (d, J = 5.9 Hz, 2 H), 4.05-4.15 (m, 2



1H-pyrazol-4-
H), 3.83 (d, J = 11.1 Hz, 1 H), 3.55-3.71 (m, 1



yl]thiophene-2-
H), 3.19-3.37 (m, 2 H), 1.68-1.85 (m, 1 H),



carboxamide
1.48-1.63 (m, 1 H), 1.32-1.50 (m, 2 H),




1.06-1.29 (m, 1 H)


200
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm




a]pyridin-6-
9.00 (t, J = 5.8 Hz, 1 H), 8.46 (s, 1 H), 8.20 (s, 1 H),



ylmethyl)-5-[1-
7.95 (s, 1 H), 7.81 (s, 1 H), 7.69 (d, J = 3.9 Hz,



(tetrahydrofuran-3-
1 H), 7.49-7.57 (m, 2 H), 7.15-7.24 (m, 2



ylmethyl)-1H-
H), 4.42 (d, J = 5.7 Hz, 2 H), 4.10 (d, J = 7.5 Hz,



pyrazol-4-
2 H), 3.69-3.79 (m, 1 H), 3.56-3.70 (m, 2



yl]thiophene-2-
H), 3.46 (dd, J = 8.7, 5.4 Hz, 2 H),



carboxamide
1.81-1.98 (m, 1 H), 1.52-1.65 (m, 1 H)


201
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm




a]pyridin-6-
8.99 (t, J = 5.8 Hz, 1 H), 8.46 (s, 1 H), 8.14 (s, 1 H),



ylmethyl)-5-[1-
7.95 (s, 1 H), 7.80 (s, 1 H), 7.69 (d, J = 3.9 Hz,



(tetrahydro-2H-
1 H), 7.48-7.58 (m, 2 H), 7.12-7.25 (m, 2



pyran-4-ylmethyl)-
H), 4.43 (d, J = 5.7 Hz, 2 H), 4.00 (d, J = 7.2 Hz,



1H-pyrazol-4-
2 H), 3.81 (dd, J = 11.3, 2.9 Hz, 2 H), 3.24 (td,



yl]thiophene-2-
J = 11.6, 1.7 Hz, 2 H), 1.91-2.18 (m, 1 H),



carboxamide
1.39 (dd, J = 12.7, 1.4 Hz, 2 H), 1.14-1.30 (m,




2 H)


206
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm




a]pyridin-6-
8.99 (t, J = 5.8 Hz, 1 H), 8.46 (s, 1 H), 8.15 (s, 1 H),



ylmethyl)-5-[1-
7.95 (s, 1 H), 7.80 (s, 1 H), 7.69 (d, J = 3.9 Hz,



(tetrahydro-2H-
1 H), 7.53 (t, J = 4.6 Hz, 2 H), 7.15-7.26 (m, 2



pyran-3-ylmethyl)-
H), 4.43 (d, J = 5.9 Hz, 2 H), 4.02 (dd, J = 7.2,



1H-pyrazol-4-
3.2 Hz, 2 H), 3.64-3.72 (m, 1 H), 3.61 (dd,



yl]thiophene-2-
J = 11.1, 3.3 Hz, 1 H), 3.15 (dd, J = 11.2, 8.8 Hz,



carboxamide
1 H), 1.96-2.18 (m, 1 H), 1.52-1.70 (m, 2




H), 1.34-1.51 (m, 1 H), 1.10-1.31 (m, 2 H)


219
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm




a]pyridin-6-
8.99 (t, J = 5.9 Hz, 1 H), 8.46 (s, 1 H), 8.10 (s, 1 H),



ylmethyl)-5-[1-
7.95 (s, 1 H), 7.79 (s, 1 H), 7.70 (d, J = 3.9 Hz,



(tetrahydrofuran-2-
1 H), 7.46-7.60 (m, 2 H), 7.11-7.26 (m, 2



ylmethyl)-1H-
H), 4.43 (d, J = 5.9 Hz, 2 H), 4.04-4.25 (m, 3



pyrazol-4-
H), 3.69-3.80 (m, 1 H), 3.62 (q, J = 7.4 Hz, 1



yl]thiophene-2-
H), 1.86-2.01 (m, 1 H), 1.68-1.84 (m, 2 H),



carboxamide
1.52-1.67 (m, 1 H)


247
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

422 (M + H)+



(tetrahydro-2H-



pyran-2-ylmethyl)-



1H-pyrazol-4-



yl]thiophene-2-



carboxamide


248
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

408 (M + H)+



(tetrahydrofuran-2-



ylmethyl)-1H-



pyrazol-4-



yl]thiophene-2-



carboxamide


252
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

408 (M + H)+



(tetrahydrofuran-3-



ylmethyl)-1H-



pyrazol-4-



yl]thiophene-2-



carboxamide


253
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.04 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 7.2, 1.1 Hz,
m/e



ylmethyl)-5-[1-
1H), 8.16 (s, 1H), 7.89 (t, J = 1.0 Hz, 1H),
422 (M + H)+



(tetrahydro-2H-
7.82 (s, 1H), 7.74 (d, J = 3.9 Hz, 1H), 7.52 (d,



pyran-3-ylmethyl)-
J = 1.4 Hz, 1H), 7.40 (s, 1H), 7.22 (d, J = 3.8 Hz,



1H-pyrazol-4-
1H), 6.85 (dd, J = 7.0, 1.7 Hz, 1H),



yl]thiophene-2-
4.48 (d, J = 5.7 Hz, 2H), 4.03 (dd, J = 7.3, 2.1 Hz,



carboxamide
2H), 3.76-3.57 (m, 2H), 3.42-3.32 (m, 1H),




3.17 (dd, J = 11.2, 8.7 Hz, 1H),




2.15-1.98 (m, 1H), 1.77-1.54 (m, 2H), 1.54-1.35 (m,




1H), 1.32-1.14 (m, 1H)


254
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-{1-[(3-

408 (M + H)+



methyloxetan-3-



yl)methyl]-1H-



pyrazol-4-



yl}thiophene-2-



carboxamide


265
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

422 (M + H)+



(tetrahydro-2H-



pyran-4-ylmethyl)-



1H-pyrazol-4-



yl]thiophene-2-



carboxamide


269
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (t, J = 5.9 Hz, 1H), 8.53-8.45 (m, 1H),
m/e



ylmethyl)-5-[1-(2-
8.13 (s, 1H), 7.89 (s, 1H), 7.81 (s, 1H), 7.74 (d, J = 3.9 Hz,
382 (M + H)+



methoxyethyl)-1H-
1H), 7.52 (d, J = 1.1 Hz, 1H), 7.40 (s,



pyrazol-4-
1H), 7.22 (d, J = 3.8 Hz, 1H), 6.85 (dd, J = 7.0,



yl]thiophene-2-
1.6 Hz, 1H), 4.48 (d, J = 5.9 Hz, 2H),



carboxamide
4.27 (t, J = 5.3 Hz, 2H), 3.70 (t, J = 5.3 Hz,




2H), 3.24 (s, 3H)


272
5-[1-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



(cyclohexylmethyl)-
9.04 (t, J = 6.1 Hz, 1H), 8.49 (d, J = 7.8 Hz, 1H),
m/e



5-ethyl-1H-
7.89 (s, 1H), 7.78 (d, J = 4.1 Hz, 1H), 7.72 (s,
448 (M + H)+



pyrazol-4-yl]-N-
1H), 7.52 (d, J = 1.0 Hz, 1H), 7.40 (s, 1H),



(imidazo[1,2-
7.17 (d, J = 4.1 Hz, 1H), 6.85 (dd, J = 7.1, 1.7 Hz,



a]pyridin-7-
1H), 4.48 (d, J = 5.8 Hz, 2H), 3.90 (d, J = 7.5 Hz,



ylmethyl)thiophene-
2H), 2.87 (q, J = 7.2 Hz, 2H),



2-carboxamide
1.79-1.95 (m, 1H), 1.59-1.73 (m, J = 3.4 Hz, 3H),




1.54 (d, J = 12.5 Hz, 2H), 1.09-1.25 (m, 6H),




0.93-1.08 (m, J = 11.9 Hz, 2H)


273
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (t, J = 5.9 Hz, 1H), 8.49 (d, J = 7.1 Hz, 1H),
m/e



ylmethyl)-5-{1-[(1-
7.89 (s, 1H), 7.79 (d, J = 3.7 Hz, 1H), 7.74 (s,
492 (M + H)+



methoxy-3,3-
1H), 7.52 (d, J = 1.0 Hz, 1H), 7.40 (s, 1H),



dimethylcyclohexyl)methyl]-
7.18 (d, J = 4.1 Hz, 1H), 6.85 (dd, J = 7.1, 1.7 Hz,



5-methyl-
1H), 4.48 (d, J = 5.8 Hz, 2H),



1H-pyrazol-4-
3.97-4.16 (m, 2H), 3.20 (s, 3H), 2.45 (s, 3H),



yl}thiophene-2-
1.64-1.78 (m, 1H), 1.27-1.59 (m, 4H), 0.99-1.24 (m,



carboxamide
3H), 0.96 (s, 3H), 0.85 (s, 3H)


293
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (s, 1H), 8.47 (t, J = 9.6 Hz, 1H), 8.17 (s, 1H),
m/e



ylmethyl)-5-(1-
7.89 (s, 1H), 7.80 (s, 1H), 7.74 (d, J = 3.9 Hz,
366 (M + H)+



propyl-1H-pyrazol-
1H), 7.52 (d, J = 1.1 Hz, 1H), 7.40 (s, 1H),



4-yl)thiophene-2-
7.22 (d, J = 3.8 Hz, 1H), 6.83 (dt, J = 14.9, 7.4 Hz,



carboxamide
1H), 4.48 (d, J = 5.9 Hz, 2H), 4.07 (t, J = 7.0 Hz,




2H), 1.81 (dd, J = 14.4, 7.2 Hz, 2H),




0.84 (t, J = 7.4 Hz, 3H)


294
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (t, J = 5.9 Hz, 1H), 8.49 (d, J = 7.0 Hz, 1H),
m/e



ylmethyl)-5-{1-[2-
8.17 (s, 1H), 7.89 (s, 1H), 7.80 (s, 1H),
437 (M + H)+



(morpholin-4-
7.74 (d, J = 3.9 Hz, 1H), 7.52 (d, J = 1.2 Hz, 1H),



yl)ethyl]-1H-
7.40 (s, 1H), 7.22 (d, J = 3.8 Hz, 1H),



pyrazol-4-
6.85 (dd, J = 7.0, 1.5 Hz, 1H), 4.48 (d, J = 5.9 Hz,



yl}thiophene-2-
2H), 4.24 (t, J = 6.5 Hz, 2H), 3.59-3.49 (m,



carboxamide
4H), 2.72 (t, J = 6.5 Hz, 2H), 2.45-2.35 (m,




4H)


295
5-(1-ethyl-1H-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



pyrazol-4-yl)-N-
9.02 (t, J = 5.9 Hz, 1H), 8.49 (d, J = 7.0 Hz, 1H),
m/e



(imidazo[1,2-
8.17 (s, 1H), 7.89 (s, 1H), 7.79 (s, 1H),
352 (M + H)+



a]pyridin-7-
7.74 (d, J = 3.8 Hz, 1H), 7.52 (d, J = 1.2 Hz, 1H),



ylmethyl)thiophene-
7.40 (s, 1H), 7.21 (d, J = 3.8 Hz, 1H),



2-carboxamide
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.48 (d, J = 5.9 Hz,




2H), 4.15 (q, J = 7.3 Hz, 2H), 1.39 (t, J = 7.3 Hz,




3H)


296
5-[1-(1,1-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



dioxidotetrahydrothiophen-
9.05 (t, J = 6.0 Hz, 1H), 8.49 (d, J = 6.9 Hz, 1H),
m/e



3-yl)-1H-
8.32 (s, 1H), 7.94 (s, 1H), 7.89 (s, 1H),
442 (M + H)+



pyrazol-4-yl]-N-
7.76 (d, J = 3.8 Hz, 1H), 7.52 (d, J = 1.1 Hz, 1H),



(imidazo[1,2-
7.40 (s, 1H), 7.26 (d, J = 3.8 Hz, 1H),



a]pyridin-7-
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 5.35-5.18 (m, 1H),



ylmethyl)thiophene-
4.48 (d, J = 5.9 Hz, 2H), 3.75 (dd, J = 13.6,



2-carboxamide
8.2 Hz, 1H), 3.48 (m, 2H), 3.35-3.20 (m,




1H), 2.78-2.53 (m, 2H)


300
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.04 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 7.0, 0.8 Hz,
m/e



ylmethyl)-5-{1-[2-
1H), 8.25 (s, 1H), 7.89 (d, J = 1.4 Hz, 2H),
430 (M + H)+



(methylsulfonyl)ethyl]-
7.75 (d, J = 3.9 Hz, 1H), 7.52 (d, J = 1.2 Hz,



1H-pyrazol-4-
1H), 7.40 (s, 1H), 7.24 (d, J = 3.8 Hz, 1H),



yl}thiophene-2-
6.85 (dd, J = 7.0, 1.7 Hz, 1H), 4.57 (t, J = 6.9 Hz,



carboxamide
2H), 4.48 (d, J = 5.9 Hz, 2H), 3.73 (t, J = 6.9 Hz,




2H), 2.93 (s, 3H)


304
5-{1-[(2R)-2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



hydroxypropyl]-
9.02 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 7.0, 0.7 Hz,
m/e



1H-pyrazol-4-yl}-
1H), 8.09 (s, 1H), 7.89 (s, 1H), 7.80 (d, J = 0.5 Hz,
382 (M + H)+



N-(imidazo[1,2-
1H), 7.74 (d, J = 3.9 Hz, 1H), 7.52 (d, J = 1.2 Hz,



a]pyridin-7-
1H), 7.40 (s, 1H), 7.22 (d, J = 3.8 Hz,



ylmethyl)thiophene-
1H), 6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.93 (d, J = 4.7 Hz,



2-carboxamide
1H), 4.48 (d, J = 5.9 Hz, 2H),




4.11-3.93 (m, 3H), 1.12-0.98 (m, 3H)


316
5-[1-(1,4-dioxan-2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



ylmethyl)-1H-
9.03 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 7.0, 0.7 Hz,
m/e



pyrazol-4-yl]-N-
1H), 8.12 (s, 1H), 7.89 (s, 1H), 7.82 (s, 1H),
424 (M + H)+



(imidazo[1,2-
7.74 (d, J = 3.8 Hz, 1H), 7.52 (d, J = 1.2 Hz,



a]pyridin-7-
1H), 7.40 (s, 1H), 7.23 (d, J = 3.8 Hz, 1H),



ylmethyl)thiophene-
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.48 (d, J = 5.9 Hz,



2-carboxamide
2H), 4.20-4.14 (m, 2H), 3.96-3.83 (m,




1H), 3.79-3.70 (m, 2H), 3.68-3.39 (m, 3H),




3.29-3.21 (m, 1H)


317
5-[1-(2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



hydroxyethyl)-1H-
9.02 (t, J = 5.9 Hz, 1H), 8.49 (dd, J = 7.0, 0.7 Hz,
m/e



pyrazol-4-yl]-N-
1H), 8.12 (s, 1H), 7.89 (d, J = 0.8 Hz, 1H),
368 (M + H)+



(imidazo[1,2-
7.80 (d, J = 0.6 Hz, 1H), 7.74 (d, J = 3.8 Hz,



a]pyridin-7-
1H), 7.52 (d, J = 1.2 Hz, 1H), 7.40 (s, 1H),



ylmethyl)thiophene-
7.22 (d, J = 3.9 Hz, 1H), 6.85 (dd, J = 7.0, 1.6 Hz,



2-carboxamide
1H), 4.92 (t, J = 5.3 Hz, 1H), 4.48 (d, J = 5.9 Hz,




2H), 4.15 (t, J = 5.6 Hz, 2H), 3.75 (q,




J = 5.5 Hz, 2H)


344
5-{1-[(1,1-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



dioxidotetrahydro-
9.04 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 7.0, 0.8 Hz,
m/e



2H-thiopyran-3-
1H), 8.19 (d, J = 0.4 Hz, 1H), 7.89 (d, J = 0.8 Hz,
470 (M + H)+



yl)methyl]-1H-
1H), 7.86 (d, J = 0.5 Hz, 1H), 7.75 (d, J = 3.9 Hz,



pyrazol-4-yl}-N-
1H), 7.52 (d, J = 1.2 Hz, 1H), 7.40 (s,



(imidazo[1,2-
1H), 7.24 (d, J = 3.9 Hz, 1H), 6.85 (dd, J = 7.0,



a]pyridin-7-
1.7 Hz, 1H), 4.48 (d, J = 5.8 Hz, 2H),



ylmethyl)thiophene-
4.13 (d, J = 6.6 Hz, 2H), 3.09-2.83 (m, 4H),



2-carboxamide
2.47-2.40 (m, 1H), 2.14-1.96 (m, 1H),




1.88-1.69 (m, 1H), 1.69-1.54 (m, 1H),




1.37-1.14 (m, 1H)


345
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (t, J = 6.0 Hz, 1H), 8.49 (d, J = 7.0 Hz, 1H),
m/e



ylmethyl)-5-(1-
8.12 (s, 1H), 7.89 (s, 1H), 7.79 (s, 1H),
338 (M + H)+



methyl-1H-pyrazol-
7.74 (d, J = 3.8 Hz, 1H), 7.52 (d, J = 1.1 Hz, 1H),



4-yl)thiophene-2-
7.40 (s, 1H), 7.21 (d, J = 3.8 Hz, 1H),



carboxamide
6.84 (dd, J = 7.0, 1.6 Hz, 1H), 4.48 (d, J = 5.9 Hz,




2H), 3.86 (s, 3H)


363
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.22 (t, J = 5.9 Hz, 1H), 8.50 (dd, J = 6.9, 0.8 Hz,
m/e



ylmethyl)-5-(1-
1H), 7.92-7.86 (m, 2H), 7.53 (d, J = 1.2 Hz,
338 (M + H)+



methyl-1H-pyrazol-
1H), 7.48 (d, J = 2.0 Hz, 1H), 7.45 (d, J = 3.9 Hz,



5-yl)thiophene-2-
1H), 7.41 (s, 1H), 6.86 (dd, J = 7.0, 1.7 Hz,



carboxamide
1H), 6.59 (d, J = 1.9 Hz, 1H), 4.51 (d, J = 5.9 Hz,




2H), 3.98 (s, 3H)


395
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 6.9, 1.0 Hz,
m/e



ylmethyl)-5-{1-
1H), 8.12 (s, 1H), 7.89 (t, J = 1.0 Hz, 1H),
408 (M + H)+



[(2R)-
7.81 (s, 1H), 7.74 (d, J = 4.0 Hz, 1H), 7.52 (d,



tetrahydrofuran-2-
J = 1.5 Hz, 1H), 7.40 (s, 1H), 7.23 (d, J = 4.0 Hz,



ylmethyl]-1H-
1H), 6.85 (dd, J = 7.0, 1.7 Hz, 1H),



pyrazol-4-
4.48 (d, J = 5.9 Hz, 2H), 4.26-4.04 (m, 3H),



yl}thiophene-2-
3.82-3.69 (m, 1H), 3.69-3.57 (m, 1H),



carboxamide
2.00-1.85 (m, 1H), 1.85-1.70 (m, 2H), 1.70-1.52 (m,




1H)


397
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.02 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 6.9, 1.0 Hz,
m/e



ylmethyl)-5-{1-
1H), 8.11 (d, J = 0.9 Hz, 1H), 7.89 (d, J = 0.9 Hz,
408 (M + H)+



[(2S)-
1H), 7.80 (d, J = 0.9 Hz, 1H), 7.74 (d, J = 3.9 Hz,



tetrahydrofuran-2-
1H), 7.52 (d, J = 1.2 Hz, 1H),



ylmethyl]-1H-
7.43-7.37 (m, 1H), 7.23 (d, J = 3.9 Hz, 1H),



pyrazol-4-
6.85 (dd, J = 7.1, 1.7 Hz, 1H), 4.48 (d, J = 5.7 Hz,



yl}thiophene-2-
2H), 4.27-4.06 (m, 3H), 3.82-3.69 (m, 1H),



carboxamide
3.69-3.58 (m, 1H), 2.01-1.86 (m, 1H),




1.86-1.69 (m, 2H), 1.69-1.52 (m, 1H)


410
N-(imidazo[1,2-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.03 (t, J = 6.0 Hz, 1H), 8.49 (d, J = 6.7 Hz, 1H),
m/e



ylmethyl)-5-[1-
8.24 (s, 1H), 7.89 (s, 1H), 7.82 (s, 1H),
408 (M + H)+



(tetrahydro-2H-
7.75 (d, J = 3.9 Hz, 1H), 7.52 (d, J = 1.1 Hz, 1H),



pyran-4-yl)-1H-
7.40 (s, 1H), 7.23 (d, J = 3.9 Hz, 1H),



pyrazol-4-
6.85 (dd, J = 7.0, 1.7 Hz, 1H), 4.54-4.34 (m, 3H),



yl]thiophene-2-
4.04-3.88 (m, 2H), 3.47 (td, J = 11.3, 3.9 Hz,



carboxamide
2H), 2.06-1.86 (m, 4H)


465
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.05 (t, J = 6.0 Hz, 1H), 8.50 (d, J = 7.0 Hz, 1H),
m/e



ylmethyl)-5-{1-[(2-
8.03 (s, 1H), 7.90 (s, 1H), 7.80 (s, 1H),
436 (M + H)+



methyltetrahydro-
7.75 (d, J = 3.8 Hz, 1H), 7.54 (d, J = 1.1 Hz, 1H),



2H-pyran-2-
7.41 (s, 1H), 7.25 (d, J = 3.9 Hz, 1H),



yl)methyl]-1H-
6.86 (dd, J = 7.0, 1.6 Hz, 1H), 4.49 (d, J = 5.9 Hz,



pyrazol-4-
2H), 4.24 (d, J = 14.1 Hz, 1H), 4.10 (d, J = 14.0 Hz,



yl}thiophene-2-
1H), 3.81-3.67 (m, 1H),



carboxamide
3.65-3.52 (m, 1H), 1.71-1.55 (m, 2H), 1.52-1.31 (m,




4H), 1.07 (s, 3H)


466
tert-butyl 4-[(4-{5-

1H NMR (300 MHz, DMSO-d6) δ ppm

(ESI(+))



[(imidazo[1,2-
9.02 (t, J = 6.0 Hz, 1H), 8.49 (dd, J = 7.1, 1.0 Hz,
m/e



a]pyridin-7-
1H), 8.14 (d, J = 0.8 Hz, 1H), 7.89 (s, 1H),
521 (M + H)+



ylmethyl)carbamoyl]thiophen-
7.81 (d, J = 0.9 Hz, 1H), 7.74 (d, J = 3.8 Hz,



2-yl}-
1H), 7.52 (d, J = 1.3 Hz, 1H), 7.40 (s, 1H),



1H-pyrazol-1-
7.22 (d, J = 3.9 Hz, 1H), 6.84 (dd, J = 7.1, 1.7 Hz,



yl)methyl]piperidine-
1H), 4.48 (d, J = 5.7 Hz, 2H), 4.02 (d, J = 7.0 Hz,



1-carboxylate
2H), 3.92 (d, J = 13.2 Hz, 2H),




2.81-2.57 (m, 2H), 2.16-1.90 (m, 1H),




1.56-1.42 (m, 2H), 1.38 (s, 9H), 1.22-0.94 (m, 2H)


475
5-[1-

(ESI(+))



(cyclobutylmethyl)-

m/e



1H-pyrazol-4-yl]-

392 (M + H)+



N-(imidazo[1,2-



a]pyridin-7-



ylmethyl)thiophene-



2-carboxamide


476
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

392 (M + H)+



(tetrahydrofuran-2-



ylmethyl)-1H-



pyrazol-4-yl]furan-



2-carboxamide


477
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

406 (M + H)+



(tetrahydro-2H-



pyran-2-ylmethyl)-



1H-pyrazol-4-



yl]furan-2-



carboxamide


478
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

392 (M + H)+



(tetrahydrofuran-3-



ylmethyl)-1H-



pyrazol-4-yl]furan-



2-carboxamide


479
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

406 (M + H)+



(tetrahydro-2H-



pyran-3-ylmethyl)-



1H-pyrazol-4-



yl]furan-2-



carboxamide


480
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

406 (M + H)+



(tetrahydro-2H-



pyran-4-ylmethyl)-



1H-pyrazol-4-



yl]furan-2-



carboxamide


481
5-[1-

(ESI(+))



(cyclobutylmethyl)-

m/e



1H-pyrazol-4-yl]-

376 (M + H)+



N-(imidazo[1,2-



a]pyridin-7-



ylmethyl)furan-2-



carboxamide


482
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-{1-[(3-

392 (M + H)+



methyloxetan-3-



yl)methyl]-1H-



pyrazol-4-yl}furan-



2-carboxamide


483
5-[1-(2-hydroxy-2-

(ESI(+))



methylpropyl)-1H-

m/e



pyrazol-4-yl]-N-

380 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)furan-2-



carboxamide


883
5-[1-(2,2-

(ESI(+))



dimethylpropyl)-

m/e



1H-pyrazol-4-yl]-

394 (M + H)+



N-(imidazo[1,2-



a]pyridin-7-



ylmethyl)thiophene-



2-carboxamide


884
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-

472 (M + H)+



(tricyclo[3.3.1.1~3,



7~]dec-1-



ylmethyl)-1H-



pyrazol-4-



yl]thiophene-2-



carboxamide


885
5-(1-benzyl-1H-

(ESI(+))



pyrazol-4-yl)-N-

m/e



(imidazo[1,2-

414 (M + H)+



a]pyridin-7-



ylmethyl)thiophene-



2-carboxamide


886
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-5-[1-(2-

474 (M + H)+



oxatricyclo[3.3.1.1~3,



7~]dec-1-



ylmethyl)-1H-



pyrazol-4-



yl]thiophene-2-



carboxamide


1082
5-{1-[2,2-dimethyl-

(ESI(+))



3-(piperazin-1-

m/e



yl)propyl]-1H-

478 (M + H)+



pyrazol-4-yl}-N-



(imidazo[1,2-



a]pyridin-7-



ylmethyl)thiophene-



2-carboxamide


1083
5-[1-(3-amino-2,2-

(ESI(+))



dimethylpropyl)-

m/e



1H-pyrazol-4-yl]-

409 (M + H)+



N-(imidazo[1,2-



a]pyridin-7-



ylmethyl)thiophene-



2-carboxamide









Example 76
2-cyclopentyl-N-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxoethyl]phenyl}acetamide
Example 76A
N-(imidazo[1,2-a]pyridin-6-yl)-2-(4-nitrophenyl)acetamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-amine for 3-methylbutan-1-amine and 2-(4-nitrophenyl)acetic acid for 4-nitrobenzoic acid.


Example 76B
2-(4-aminophenyl)-N-(imidazo[1,2-a]pyridin-6-yl)acetamide

The title compound was prepared as described in Example 1B, substituting N-(imidazo[1,2-a]pyridin-6-yl)-2-(4-nitrophenyl)acetamide for N-isopentyl-4-nitrobenzamide.


Example 76C
2-cyclopentyl-N-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxoethyl]phenyl}acetamide

The title compound was prepared as described in Example 52A, substituting 2-(4-aminophenyl)-N-(imidazo[1,2-a]pyridin-6-yl)acetamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.71 (s, 1H), 9.83 (s, 1H), 9.55 (m, 1H), 8.38 (d, J=2.0 Hz, 1H), 8.08 (d, J=2.0 Hz, 1H), 7.96-7.88 (m, 1H), 7.80-7.73 (m, 1H), 7.58-7.51 (m, 2H), 7.29-7.23 (m, 2H), 3.67 (bs, 2H), 2.34-2.15 (m, 3H), 1.82-1.65 (m, 2H), 1.67-1.41 (m, 4H), 1.26-1.10 (m, 2H); MS (ESI(+)) m/e 377 (M+H)+.


Example 77
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide
Example 77A
tert-butyl 4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)phenylcarbamate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(tert-butoxycarbonylamino)benzoic acid for 4-nitrobenzoic acid.


Example 77B
4-amino-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)phenylcarbamate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 77C
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-2-ylacetyl)amino]benzamide

The title compound was prepared as described in Example 1A, substituting 4-amino-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide for 3-methylbutan-1-amine and 2-(tetrahydrofuran-2-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.14 (s, 1H), 8.93 (t, J=5.8 Hz, 1H), 8.48-8.45 (m, 1H), 7.95 (s, 1H), 7.88-7.82 (m, 2H), 7.71-7.64 (m, 2H), 7.53 (m, 7.55-7.48, 2H), 7.22 (dd, J=9.2, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 4.23-4.12 (m, 1H), 3.82-3.72 (m, 1H), 3.66-3.56 (m, 1H), 2.59-2.44 (m, 2H), 2.07-1.95 (m, 1H), 1.92-1.77 (m, 2H), 1.60-1.47 (m, 1H); MS (ESI(+)) m/e 379 (M+H)+.


Example 78
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide

The title compound was prepared as described in Example 77, substituting 2-(tetrahydrofuran-3-yl)acetic acid for 2-(tetrahydrofuran-2-yl)acetic acid in Example 77C. 1H NMR (500 MHz, DMSO-d6, Temp=90° C.) δ ppm 9.87 (bs, 1H), 8.65-8.59 (m, 1H), 8.42 (s, 1H), 7.87 (s, 1H), 7.84-7.79 (m, 2H), 7.66-7.61 (m, 2H), 7.52-7.45 (m, 2H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 3.85-3.78 (m, 1H), 3.77-3.69 (m, 1H), 3.68-3.60 (m, 1H), 3.38-3.31 (m, 1H), 2.64-2.54 (m, 1H), 2.45-2.40 (m, 2H), 2.09-1.98 (m, 1H), 1.63-1.51 (m, 1H); MS (ESI(+)) m/e 379 (M+H)+.


Example 79
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide

The title compound was prepared as described in Example 77, substituting 2-(tetrahydro-2H-pyran-4-yl)acetic acid for 2-(tetrahydrofuran-2-yl)acetic acid in Example 77C. 1H NMR (500 MHz, DMSO-d6, Temp=90° C.) δ ppm 9.84 (bs, 1H), 8.67-8.60 (m, 1H), 8.42 (s, 1H), 7.87 (s, 1H), 7.85-7.79 (m, 2H), 7.67-7.61 (m, 2H), 7.52-7.45 (m, 2H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 3.85-3.77 (m, 2H), 3.35-3.26 (m, 2H), 2.28 (d, J=7.0 Hz, 2H), 2.07-1.96 (m, 1H), 1.65-1.57 (m, 2H), 1.31-1.22 (m, 2H); MS (ESI(+)) m/e 393 (M+H)+.


Example 80
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[(morpholin-4-ylacetyl)amino]benzamide

The title compound was prepared as described in Example 77, substituting 2-morpholinoacetic acid for 2-(tetrahydrofuran-2-yl)acetic acid in Example 77C. 1H NMR (500 MHz, DMSO-d6, Temp=90° C.) δ ppm 9.70 (bs, 1H), 8.69-8.63 (m, 1H), 8.42 (s, 1H), 7.90-7.81 (m, 3H), 7.70-7.65 (m, 2H), 7.53-7.45 (m, 2H), 7.21 (dd, J=9.3, 1.7 Hz, 1H), 4.46 (d, J=5.8 Hz, 2H), 3.67-3.61 (m, 4H), 3.14 (s, 2H), 2.56-2.52 (m, 4H); MS (ESI(+)) m/e 394 (M+H)+.


Example 81
4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 77, substituting 4-cyclopentylbutanoic acid for 2-(tetrahydrofuran-2-yl)acetic acid in Example 77C. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.10 (s, 1H), 8.92 (t, J=5.8 Hz, 1H), 8.46 (dd, J=1.9, 0.9 Hz, 1H), 7.95 (dd, J=1.2, 0.6 Hz, 1H), 7.87-7.81 (m, 2H), 7.70-7.64 (m, 2H), 7.55-7.49 (m, 2H), 7.22 (dd, J=9.2, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 2.37-2.30 (m, 2H), 1.81-1.68 (m, 3H), 1.64-1.41 (m, 6H), 1.19-1.02 (m, 2H); MS (ESI(+)) m/e 391 (M+H)+.


Example 82
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[(propan-2-yloxy)acetyl]amino}benzamide

The title compound was prepared as described in Example 77, substituting 2-isopropoxyacetic acid for 2-(tetrahydrofuran-2-yl)acetic acid in Example 77C. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 8.95 (t, J=5.8 Hz, 1H), 8.49-8.44 (m, 1H), 7.97-7.93 (m, 1H), 7.89-7.83 (m, 2H), 7.78-7.72 (m, 2H), 7.56-7.50 (m, 2H), 7.22 (dd, J=9.2, 1.7 Hz, 1H), 4.46 (d, J=5.8 Hz, 2H), 4.04 (s, 2H), 3.75-3.64 (m, 1H), 1.17 (d, J=6.1 Hz, 6H); MS (ESI(+)) m/e 367 391 (M+H)+.


Example 83
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate
Example 83A
4-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-bromobenzoic acid for 4-nitrobenzoic acid.


Example 83B
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.9 Hz, 1H), 8.49-8.45 (m, 1H), 7.97-7.93 (m, 1H), 7.91-7.84 (m, 2H), 7.61-7.48 (m, 4H), 7.22 (dd, J=9.3, 1.7 Hz, 1H), 6.32-6.25 (m, 1H), 4.47 (d, J=5.8 Hz, 2H), 4.05-3.99 (m, 2H), 3.58-3.50 (m, 2H), 2.55-2.44 (m, 2H), 1.43 (s, 9H); MS (ESI(+)) m/e 433 (M+H)+.


Example 84
N-{4-[(cyclopentylacetyl)amino]benzyl}imidazo[1,2-a]pyridine-6-carboxamide
Example 84A
N-(4-nitrobenzyl)imidazo[1,2-a]pyridine-6-carboxamide

The title compound was prepared as described in Example 1A, substituting (4-nitrophenyl)methanamine for 3-methylbutan-1-amine and imidazo[1,2-a]pyridine-6-carboxylic acid for 4-nitrobenzoic acid.


Example 84B
N-(4-aminobenzyl)imidazo[1,2-a]pyridine-6-carboxamide

The title compound was prepared as described in Example 1B, substituting N-(4-nitrobenzyl)imidazo[1,2-a]pyridine-6-carboxamide for N-isopentyl-4-nitrobenzamide.


Example 84C
N-{4-[(cyclopentylacetyl)amino]benzyl}imidazo[1,2-a]pyridine-6-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-aminobenzyl)imidazo[1,2-a]pyridine-6-carboxamide for 3-methylbutan-1-amine and 2-cyclopentylacetic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.80 (s, 1H), 9.16-9.11 (m, 1H), 9.04 (t, J=5.9 Hz, 1H), 8.08-8.03 (m, 1H), 7.76-7.57 (m, 3H), 7.58-7.50 (m, 2H), 7.29-7.22 (m, 2H), 4.44 (d, J=5.8 Hz, 2H), 2.33-2.14 (m, 3H), 1.81-1.67 (m, 2H), 1.66-1.42 (m, 4H), 1.27-1.09 (m, 2H); MS (ESI(+)) m/e 377 (M+H)+.


Example 85
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-1,3-thiazole-5-carboxamide
Example 85A
2-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 2-bromothiazole-5-carboxamide for 4-nitrobenzoic acid.


Example 85B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 53B, substituting 2,3,4,5-tetrahydro-1H-benzo[d]azepine for 4-cyanobenzylamine and 2-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiazole-5-carboxamide for 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.78 (t, J=5.8 Hz, 1H), 8.44 (s, 1H), 7.95 (s, 1H), 7.86 (s, 1H), 7.48-7.56 (m, 2H), 7.08-7.22 (m, 5H), 4.38 (d, J=5.9 Hz, 2H), 3.67-3.78 (m, 4H), 2.89-3.01 (m, 4H); MS (ESI(+)) m/e 402 (M+H)+.


Example 86
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-(3-phenylpyrrolidin-1-yl)-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 85, substituting 3-phenylpyrrolidine for 2,3,4,5-tetrahydro-1H-benzo[d]azepine in Example 85B. 1H NMR (400 MHz, DMSO-d6) δ 8.75 (dd, J=5.8, 5.6 Hz, 1H), 8.44 (s, 1H), 7.95 (s, 1H), 7.86 (s, 1H), 7.56-7.50 (m, 2H), 7.35-7.31 (m, 2H), 7.29-7.21 (m, 2H), 7.18 (dd, J=8.4, 4.7 Hz, 1H), 4.45 (s, 1H), 4.38 (d, J=5.8 Hz, 2H), 3.92-3.83 (m, 2H), 3.62-3.45 (m, 2H), 2.68-2.62 (m, 1H), 2.42-2.30 (m, 1H), 2.20-2.07 (m, 1H). MS (ESI)(+)) m/e 404 (M+H)+.


Example 87
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 85, substituting 3-methylbutan-1-amine for 2,3,4,5-tetrahydro-1H-benzo[d]azepine in Example 85B. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.67 (t, J=5.9 Hz, 1H), 8.42 (s, 1H), 8.08 (t, J=5.4 Hz, 1H), 7.94 (s, 1H), 7.71 (s, 1H), 7.49-7.55 (m, 2H), 7.16 (dd, J=9.3, 1.6 Hz, 1H), 4.36 (d, J=5.9 Hz, 2H), 3.17-3.26 (m, 2H), 1.61 (dq, J=6.7 Hz, 1H), 1.41 (q, J=7.0 Hz, 2H), 0.87 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 344 (M+H)+.


Example 88
2-(1,3-dihydro-2H-isoindol-2-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 85, substituting isoindoline for 2,3,4,5-tetrahydro-1H-benzo[d]azepine in Example 85B. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.81 (t, J=5.9 Hz, 1H), 8.45 (s, 1H), 7.89-7.99 (m, 2H), 7.49-7.56 (m, 2H), 7.37-7.45 (m, 2H), 7.30-7.37 (m, 2H), 7.19 (dd, J=9.3, 1.5 Hz, 1H), 4.76 (s, 4H), 4.40 (d, J=5.7 Hz, 2H); MS (ESI(+)) m/e 376 (M+H)+.


Example 89
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylcarbamoyl)amino]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.98-8.94 (m, 1H), 8.67 (s, 1H), 8.64 (s, 1H), 7.97-7.93 (m, 1H), 7.54-7.48 (m, 2H), 7.42-7.36 (m, 2H), 7.19-7.12 (m, 2H), 7.08 (dd, J=9.5, 2.1 Hz, 1H), 4.14-3.99 (m, 2H), 2.89-2.56 (m, 3H), 1.77-1.69 (m, 2H), 1.52-1.36 (m, 11H); MS (ESI(+)) m/e 436 (M+H)+.


Example 90
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide
Example 90A
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 90B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6, Temp=90° C.) δ ppm 8.75-8.67 (m, 1H), 8.43 (s, 1H), 7.89-7.83 (m, 3H), 7.54-7.43 (m, 4H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 6.29-6.23 (m, 1H), 4.47 (d, J=5.8 Hz, 2H), 4.19-4.13 (m, 2H), 3.70 (t, J=5.7 Hz, 2H), 2.95-2.84 (m, 1H), 2.57-2.49 (m, 2H), 1.04 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 403 (M+H)+.


Table 7.


The following Examples were prepared essentially as described in Example 90, substituting the appropriate carboxylic acid for isobutyric acid in Example 90B.















Ex
Name

1H NMR

MS


















91
4-[1-(2-hydroxy-2-

(ESI(+))



methylpropanoyl)-

m/e



1,2,3,6-

419 (M + H)+



tetrahydropyridin-4-



yl]-N-(imidazo[1,2-



a]pyridin-6-



ylmethyl)benzamide


92
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-4-[1-

460 (M + H)+



(morpholin-4-



ylacetyl)-1,2,3,6-



tetrahydropyridin-4-



yl]benzamide


93
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-4-[1-

459 (M + H)+



(tetrahydro-2H-



pyran-4-ylacetyl)-



1,2,3,6-



tetrahydropyridin-4-



yl]benzamide


94
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-4-[1-

445 (M + H)+



(tetrahydrofuran-3-



ylacetyl)-1,2,3,6-



tetrahydropyridin-4-



yl]benzamide


95
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-4-[1-

445 (M + H)+



(tetrahydrofuran-2-



ylacetyl)-1,2,3,6-



tetrahydropyridin-4-



yl]benzamide


96
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-

m/e



ylmethyl)-4-{1-[3-

459 (M + H)+



(tetrahydrofuran-2-



yl)propanoyl]-



1,2,3,6-



tetrahydropyridin-4-



yl}benzamide


97
4-[1-

1H NMR (300 MHz, methanol-d4) δ ppm

(ESI(+))



(cyclopentylacetyl)-
8.81-8.76 (m, 1H), 8.21 (m, 1H), 8.05-7.98 (m,
m/e



1,2,3,6-
2H), 7.97-7.79 (m, 3H), 7.59-7.53 (m, 2H),
443 (M + H)+



tetrahydropyridin-4-
6.31-6.23 (m, 1H), 4.74-4.65 (m, 2H),



yl]-N-(imidazo[1,2-
4.29-4.19 (m, 2H), 3.85-3.75 (m, 2H),



a]pyridin-6-
2.71-2.41 (m, 4H), 2.33-2.14 (m, 1H),



ylmethyl)benzamide
1.92-1.74 (m, 2H), 1.76-1.49 (m, 4H), 1.32-1.13 (m,




2H)


98
N-(imidazo[1,2-

1H NMR (300 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.81-8.76 (m, 1H), 8.21 (m, 1H), 8.05-7.98 (m,
m/e



ylmethyl)-4-{1-
2H), 7.95-7.83 (m, 3H), 7.61-7.51 (m, 2H),
443 (M + H)+



[(propan-2-
6.31-6.22 (m, 1H), 4.74-4.68 (m, 2H),



yloxy)acetyl]-
4.32-4.17 (m, 4H), 3.90-3.64 (m, 3H),



1,2,3,6-
2.73-2.53 (m, 2H), 1.25-1.16 (m, 6H)



tetrahydropyridin-4-



yl}benzamide


99
N-(imidazo[1,2-

1H NMR (300 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.81-8.77 (m, 1H), 8.22-8.20 (m, 1H),
m/e



ylmethyl)-4-[1-
8.02-7.99 (m, 2H), 7.97-7.82 (m, 3H),
431 (M + H)+



(tetrahydrofuran-2-
7.59-7.53 (m, 2H), 6.31-6.23 (m, 1H), 4.82-4.74 (m,



ylcarbonyl)-1,2,3,6-
1H), 4.70 (s, 2H), 4.40-4.11 (m, 2H),



tetrahydropyridin-4-
4.01-3.71 (m, 4H), 2.74-2.52 (m, 2H),



yl]benzamide
2.30-2.17 (m, 1H), 2.17-1.84 (m, 3H)


100
N-(imidazo[1,2-

1H NMR (300 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.81-8.77 (m, 1H), 8.24-8.17 (m, 1H),
m/e



ylmethyl)-4-[1-
8.05-7.97 (m, 2H), 7.97-7.82 (m, 3H),
431 (M + H)+



(tetrahydrofuran-3-
7.59-7.53 (m, 2H), 6.31-6.25 (m, 1H), 4.72 (s, 2H),



ylcarbonyl)-1,2,3,6-
4.35-4.21 (m, 2H), 4.06-3.93 (m, 1H),



tetrahydropyridin-4-
3.95-3.76 (m, 5H), 3.60-3.42 (m, 1H),



yl]benzamide
2.71-2.52 (m, 2H), 2.27-2.02 (m, 2H)


101
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.81-8.78 (m, 1H), 8.23-8.19 (m, 1H),
m/e



ylmethyl)-4-[1-
8.05-7.98 (m, 2H), 7.93-7.84 (m, 3H),
828 (M + H)+



(tetrahydro-2H-
7.59-7.53 (m, 2H), 6.31-6.25 (m, 1H), 4.70 (s, 2H),



pyran-4-
4.36-4.30 (m, 1H), 4.25-4.19 (m, 1H),



ylcarbonyl)-1,2,3,6-
4.02-3.93 (m, 2H), 3.87-3.78 (m, 2H),



tetrahydropyridin-4-
3.59-3.46 (m, 2H), 3.10-2.92 (m, 1H),



yl]benzamide
2.70-2.53 (m, 2H), 1.91-1.72 (m, 2H), 1.73-1.57 (m,




2H)


102
4-[1-(1,4-dioxan-2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



ylcarbonyl)-1,2,3,6-
8.79 (s, 1H), 8.23-8.20 (m, 1H), 8.04-7.99 (m,
m/e



tetrahydropyridin-4-
2H), 7.93-7.84 (m, 3H), 7.59-7.53 (m, 2H),
447 (M + H)+



yl]-N-(imidazo[1,2-
6.29-6.23 (m, 1H), 4.73-4.67 (m, 2H),



a]pyridin-6-
4.53-4.06 (m, 3H), 3.96-3.59 (m, 8H),



ylmethyl)benzamide
2.76-2.53 (m, 2H)


103
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.79 (s, 1H), 8.24-8.19 (m, 1H), 8.01 (m, 2H),
m/e



ylmethyl)-4-{1-[(2-
7.97-7.82 (m, 3H), 7.59-7.53 (m, 2H),
449 (M + H)+



methoxyethoxy)acetyl]-
6.31-6.23 (m, 1H), 4.76-4.69 (m, 2H),



1,2,3,6-
4.35-4.26 (m, 2H), 4.25-4.19 (m, 2H),



tetrahydropyridin-4-
3.86-3.62 (m, 4H), 3.61-3.54 (m, 2H), 3.35 (s, 3H),



yl}benzamide
2.72-2.54 (m, 2H)


104
4-(1-benzoyl-

1H NMR (400 MHz, DMSO-d6, Temp = 90° C.)

(ESI(+))



1,2,3,6-
δ ppm 8.89-8.82 (m, 1H), 8.73 (s, 1H),
m/e



tetrahydropyridin-4-
8.22 (d, J = 1.9 Hz, 1H), 7.96 (d, J = 1.9 Hz, 1H),
437 (M + H)+



yl)-N-(imidazo[1,2-
7.90-7.75 (m, 4H), 7.56-7.49 (m, 2H),



a]pyridin-6-
7.49-7.37 (m, 5H), 6.27 (bs, 1H), 4.58 (d, J = 5.8 Hz,



ylmethyl)benzamide
2H), 4.23-4.17 (m, 2H), 3.72-3.65 (m,




2H), 2.61-2.53 (m, 2H)


105
4-{1-[(4,4-

1H NMR (400 MHz, DMSO-d6, Temp = 90° C.)

(ESI(+))



difluorocyclohexyl)carbonyl]-
δ ppm 8.90-8.83 (m, 1H), 8.74 (s, 1H),
m/e



1,2,3,6-
8.22 (d, J = 1.9 Hz, 1H), 7.97 (d, J = 1.9 Hz, 1H),
479 (M + H)+



tetrahydropyridin-4-
7.90-7.75 (m, 4H), 7.54-7.48 (m, 2H),



yl}-N-(imidazo[1,2-
6.30-6.24 (m, 1H), 4.58 (d, J = 5.8 Hz, 2H),



a]pyridin-6-
4.21-4.15 (m, 2H), 3.77-3.69 (m, 2H),



ylmethyl)benzamide
2.91-2.79 (m, 1H), 2.58-2.51 (m, 2H),




2.12-2.00 (m, 2H), 2.00-1.59 (m, 6H)









Example 106
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea
Example 106A
1-(imidazo[1,2-a]pyridin-6-yl)-3-(4-(piperidin-4-yl)phenyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 106B
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 1A, substituting 1-(imidazo[1,2-a]pyridin-6-yl)-3-(4-(piperidin-4-yl)phenyl)urea for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6, Temp=90° C.) δ ppm 8.86-8.81 (m, 1H), 8.41 (s, 1H), 8.38 (s, 1H), 7.86 (s, 1H), 7.50-7.42 (m, 2H), 7.40-7.34 (m, 2H), 7.18-7.12 (m, 2H), 7.12-7.06 (m, 1H), 4.41-4.18 (m, 2H), 2.95-2.64 (m, 4H), 1.87-1.78 (m, 2H), 1.56-1.38 (m, 2H), 1.03 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 406 (M+H)+.


Example 108
2-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 85, substituting 1,2,3,4-tetrahydroisoquinoline for 2,3,4,5-tetrahydro-1H-benzo[d]azepine in Example 85B. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.81 (t, J=5.8 Hz, 1H), 8.47 (s, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.48-7.63 (m, 2H), 7.13-7.32 (m, 5H), 4.65 (s, 2H), 4.39 (d, J=5.9 Hz, 2H), 3.73 (t, J=6.0 Hz, 2H), 2.94 (t, J=6.0 Hz, 2H); MS (ESI(+)) m/e 390 (M+H)+.


Example 109
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 106, substituting tetrahydro-2H-pyran-4-carboxylic acid for isobutyric acid in Example 106B. 1H NMR (400 MHz, methanol-d4) δ ppm 9.37-9.33 (m, 1H), 8.22-8.17 (m, 1H), 7.97 (d, J=2.1 Hz, 1H), 7.89-7.77 (m, 2H), 7.44-7.38 (m, 2H), 7.24-7.18 (m, 2H), 4.73-4.64 (m, 1H), 4.25-4.15 (m, 1H), 4.01-3.93 (m, 2H), 3.57-3.46 (m, 2H), 3.27-3.17 (m, 1H), 3.06-2.95 (m, 1H), 2.87-2.66 (m, 2H), 2.00-1.70 (m, 4H), 1.70-1.48 (m, 4H); MS (ESI(+)) m/e 448 (M+H)+.


Example 110
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 106, substituting 2-(tetrahydrofuran-3-yl)acetic acid for isobutyric acid in Example 106B. 1H NMR (400 MHz, methanol-d4) δ ppm 9.37-9.32 (m, 1H), 8.21-8.17 (m, 1H), 7.97 (d, J=2.1 Hz, 1H), 7.88-7.76 (m, 2H), 7.44-7.38 (m, 2H), 7.23-7.18 (m, 2H), 4.71-4.62 (m, 1H), 4.14-4.05 (m, 1H), 3.95-3.82 (m, 2H), 3.81-3.70 (m, 1H), 3.47-3.35 (m, 1H), 3.25-3.12 (m, 1H), 2.86-2.48 (m, 5H), 2.22-2.07 (m, 1H), 1.95-1.83 (m, 2H), 1.74-1.46 (m, 3H); MS (ESI(+)) m/e 448 (M+H)+.


Example 111
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 106, substituting 2-(tetrahydrofuran-2-yl)acetic acid for isobutyric acid in Example 106B. 1H NMR (400 MHz, methanol-d4) δ ppm 9.37-9.32 (m, 1H), 8.21-8.17 (m, 1H), 7.99-7.95 (m, 1H), 7.88-7.77 (m, 2H), 7.44-7.38 (m, 2H), 7.23-7.17 (m, 2H), 4.73-4.63 (m, 1H), 4.33-4.20 (m, 1H), 4.19-4.10 (m, 1H), 3.92-3.83 (m, 1H), 3.79-3.69 (m, 1H), 3.26-3.14 (m, 1H), 2.87-2.65 (m, 3H), 2.63-2.47 (m, 1H), 2.19-2.06 (m, 1H), 2.01-1.81 (m, 4H), 1.77-1.50 (m, 3H); MS (ESI(+)) m/e 448 (M+H)+.


Example 112
1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-imidazo[1,2-a]pyridin-6-ylurea

The title compound was prepared as described in Example 106, substituting benzoic acid for isobutyric acid in Example 106B. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.87-8.81 (m, 1H), 8.38 (bs, 1H), 8.38 (bs, 1H), 7.86 (s, 1H), 7.51-7.34 (m, 9H), 7.21-7.14 (m, 2H), 7.09 (dd, J=9.5, 2.0 Hz, 1H), 4.34-3.97 (m, 2H), 3.08-2.95 (m, 2H), 2.83-2.71 (m, 1H), 1.85-1.77 (m, 2H), 1.66-1.50 (m, 2H); MS (ESI(+)) m/e 440 (M+H)+.


Example 113
1-imidazo[1,2-a]pyridin-6-yl-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 106, substituting tetrahydrofuran-2-carboxylic acid for isobutyric acid in Example 106B. 1H NMR (400 MHz, methanol-d4) δ ppm 9.38-9.33 (m, 1H), 8.21-8.16 (m, 1H), 8.00-7.95 (m, 1H), 7.88-7.77 (m, 2H), 7.44-7.38 (m, 2H), 7.23-7.17 (m, 2H), 4.83-4.73 (m, 1H), 4.69-4.60 (m, 1H), 4.22-4.11 (m, 1H), 4.01-3.90 (m, 1H), 3.91-3.82 (m, 1H), 3.26-3.12 (m, 1H), 2.87-2.68 (m, 2H), 2.31-2.14 (m, 1H), 2.12-1.75 (m, 5H), 1.77-1.50 (m, 2H); MS (ESI(+)) m/e 434 (M+H)+.


Example 114
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.40 (s, 1H), 7.86-7.79 (m, 3H), 7.52 (t, J=5.4 Hz, 2H), 7.34 (dd, J=9.3, 1.7 Hz, 1H), 7.06-6.99 (m, 2H), 4.72-4.60 (m, 1H), 4.56 (s, 2H), 3.77-3.65 (m, 2H), 3.41-3.30 (m, 2H), 2.03-1.90 (m, 2H), 1.76-1.59 (m, 2H), 1.46 (s, 9H); MS (ESI(+)) m/e 451 (M+H)+.


Example 115
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide
Example 115A
2-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 2-bromothiazole-5-carboxylic acid for 4-nitrobenzoic acid.


Example 115B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-((tetrahydrofuran-2-yl)methylamino)thiazole-5-carboxamide

The title compound was prepared as in Example 53B, substituting (tetrahydrofuran-2-yl)methanamine for 4-cyanobenzylamine and 2-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiazole-5-carboxamide for 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide.


Example 115C
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[{[2-(propan-2-yloxy)ethyl]carbamoyl}(tetrahydrofuran-2-ylmethyl)amino]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1C, substituting 2-isopropoxyethanamine for 4-amino-N-isopentylbenzamide and N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-((tetrahydrofuran-2-yl)methylamino)thiazole-5-carboxamide for imidazo[1,2-a]pyridin-6-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.52 (s, 1H), 8.21 (d, J=9.0 Hz, 1H), 7.96 (s, 1H), 7.89 (d, J=1.5 Hz, 1H), 7.86-7.80 (m, 1H), 7.78 (d, J=9.5 Hz, 1H), 7.73 (s, 1H), 6.96-6.86 (m, 1H), 4.74-4.60 (m, 2H), 4.50-4.38 (m, 1H), 4.26 (ddd, J=4.4, 2.2, 0.6 Hz, 1H), 4.07-3.90 (m, 2H), 3.85-3.74 (m, 1H), 3.63 (dd, J=12.2, 6.1 Hz, 1H), 3.60-3.53 (m, 2H), 3.53-3.41 (m, 2H), 1.95 (dd, J=7.8, 6.9 Hz, 3H), 1.63-1.56 (m, 1H), 1.18 (dd, J=6.1, 1.2 Hz, 6H); (APCI(+)) m/e 487 (M+H)+.


Table 8.


The following Examples were prepared essentially as described in Example 115, substituting the appropriate amine in Example 115B and the appropriate amine for 2-isopropoxyethanamine in Example 115C.















Ex
Name

1H NMR

MS







138
N-(imidazo[1,2-

1H NMR (400 MHz, CDCl3) δ ppm 8.09 (d,

(APCI(+))



a]pyridin-7-
J = 7.0 Hz, 1H), 7.86 (d, J = 14.0 Hz, 2H),
m/e



ylmethyl)-2-{[(2-
7.62 (d, J = 0.8 Hz, 1H), 7.54 (d, J = 9.1 Hz,
459 (M + H)+



methoxyethyl)carbamoyl](tetrahydrofuran-
2H), 6.84 (dd, J = 7.0, 1.4 Hz, 1H), 6.27 (t,



2-
J = 5.8 Hz, 1H), 4.63 (d, J = 6.0 Hz, 2H),



ylmethyl)amino}-
4.44 (d, J = 14.3 Hz, 1H), 4.29 (q, J = 7.3 Hz,



1,3-thiazole-5-
1H), 4.05 (dd, J = 15.4, 7.2 Hz, 1H),



carboxamide
3.92 (dd, J = 15.2, 7.2 Hz, 1H),




3.86-3.72 (m, 1H), 3.58-3.51 (m, 2H), 3.48 (dd, J = 9.2,




3.8 Hz, 3H), 3.39 (s, 3H), 2.14 (dt, J = 12.4,




6.3 Hz, 1H), 2.05-1.86 (m, 2H)


141
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.78 (s, 1H), 8.22 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-{[(2-
8.03 (d, J = 2.1 Hz, 1H), 7.99 (d, J = 9.8 Hz,
459 (M + H)+



methoxyethyl)carbamoyl](tetrahydrofuran-
2H), 7.91 (d, J = 9.3 Hz, 1H), 4.65 (s, 2H),



3-
4.24 (dd, J = 15.2, 7.6 Hz, 1H), 4.12 (dd, J = 15.2,



ylmethyl)amino}-
7.9 Hz, 1H), 3.93 (td, J = 8.1, 5.8 Hz,



1,3-thiazole-5-
1H), 3.79-3.67 (m, 2H), 3.60 (dd, J = 8.7,



carboxamide
5.2 Hz, 1H), 3.55-3.45 (m, 4H),




3.36 (s, 3H), 2.85-2.75 (m, 1H), 2.00 (td, J = 13.4,




7.8 Hz, 1H), 1.72 (dt, J = 20.1, 6.3 Hz,




1H)


151
N-(imidazo[1,2-

1H NMR (500 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.77 (s, 1H), 8.21 (d, J = 2.0 Hz, 1H),
m/e



ylmethyl)-2-{[(2-
8.02 (d, J = 2.1 Hz, 1H), 7.99 (dd, J = 9.3, 1.4 Hz,
473 (M + H)+



methoxyethyl)carbamoyl](tetrahydro-
1H), 7.97 (s, 1H), 7.90 (d, J = 9.3 Hz,



2H-pyran-4-
1H), 4.65 (s, 2H), 4.07 (d, J = 7.6 Hz, 2H),



ylmethyl)amino}-
3.92 (dd, J = 11.5, 3.0 Hz, 2H), 3.52 (dd, J = 8.3,



1,3-thiazole-5-
3.1 Hz, 2H), 3.47 (dd, J = 8.1, 3.0 Hz,



carboxamide
2H), 3.36 (s, 3H), 3.36-3.32 (m, 2H),




2.14 (ddd, J = 15.4, 7.7, 3.8 Hz, 1H), 1.54 (d, J = 11.2 Hz,




2H), 1.42 (qd, J = 12.1, 4.4 Hz,




2H)


152
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.78 (s, 1H), 8.22 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-[{[2-
8.03 (d, J = 2.1 Hz, 1H), 8.01-7.97 (m, 2H),
501 (M + H)+



(propan-2-
7.91 (d, J = 9.3 Hz, 1H), 4.65 (s, 2H),



yloxy)ethyl]carbamoyl}(tetrahydro-
4.06 (d, J = 7.6 Hz, 2H), 3.92 (dd, J = 11.4, 3.0 Hz,



2H-
2H), 3.63 (dt, J = 12.2, 6.1 Hz, 1H),



pyran-4-
3.57 (dd, J = 10.1, 4.5 Hz, 2H), 3.45 (t, J = 5.5 Hz,



ylmethyl)amino]-
2H), 3.35 (dd, J = 11.6, 1.7 Hz, 2H),



1,3-thiazole-5-
2.16 (ddd, J = 11.4, 7.6, 3.8 Hz, 1H),



carboxamide
1.55 (dd, J = 12.6, 1.5 Hz, 2H), 1.42 (qd, J = 12.1,




4.4 Hz, 2H), 1.16 (d, J = 6.1 Hz, 6H)


153
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.70 (s, 1H), 8.14 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-{[(2-
7.95 (d, J = 2.2 Hz, 1H), 7.91 (dd, J = 9.4, 1.5 Hz,
459 (M + H)+



methoxyethyl)carbamoyl][(2R)-
1H), 7.88 (s, 1H), 7.82 (d, J = 9.3 Hz,



tetrahydrofuran-2-
1H), 4.57 (s, 2H), 4.33 (dd, J = 15.4, 1.8 Hz,



ylmethyl]amino}-
1H), 4.17 (dd, J = 11.3, 4.9 Hz, 1H),



1,3-thiazole-5-
4.00 (dd, J = 15.4, 7.7 Hz, 1H), 3.86 (dd, J = 15.2,



carboxamide
7.0 Hz, 1H), 3.71 (td, J = 7.8, 5.8 Hz,




1H), 3.52-3.39 (m, 2H),




3.38-3.32 (m, 2H), 3.30 (s, 3H), 2.11-1.95 (m, 1H),




1.95-1.77 (m, 2H), 1.66-1.48 (m, 1H),




0.99-0.87 (m, 1H)


154
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.77 (s, 1H), 8.21 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-({[2-
8.02 (d, J = 2.1 Hz, 1H), 7.98 (dd, J = 9.4, 1.2 Hz,
487 (M + H)+



(propan-2-
1H), 7.96 (s, 1H), 7.90 (d, J = 9.3 Hz,



yloxy)ethyl]carbamoyl}[(2R)-
1H), 4.64 (s, 2H), 4.41 (dd, J = 15.4, 1.6 Hz,



tetrahydrofuran-2-
1H), 4.29-4.21 (m, 1H), 4.07 (dd, J = 15.4,



ylmethyl]amino)-
7.6 Hz, 1H), 3.96 (dd, J = 15.0, 7.1 Hz,



1,3-thiazole-5-
1H), 3.77 (dd, J = 14.0, 7.7 Hz, 1H),



carboxamide
3.64 (dt, J = 12.2, 6.1 Hz, 1H), 3.57 (t, J = 5.0 Hz,




2H), 3.41 (t, J = 5.3 Hz, 2H),




2.15-2.03 (m, 1H), 2.00-1.87 (m, 2H), 1.64 (dq,




J = 12.4, 8.2 Hz, 1H), 1.16 (d, J = 6.1 Hz,




6H)


155
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.78 (s, 1H), 8.21 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-{[(2-
8.03 (d, J = 2.1 Hz, 1H), 8.01-7.97 (m, 1H),
459 (M + H)+



methoxyethyl)carbamoyl][(2S)-
7.96 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H),



tetrahydrofuran-2-
4.64 (s, 2H), 4.41 (d, J = 15.4 Hz, 1H), 4.26 (q, J = 6.4 Hz,



ylmethyl]amino}-
1H), 4.08 (dd, J = 15.4, 7.7 Hz,



1,3-thiazole-5-
1H), 3.94 (dd, J = 15.1, 7.1 Hz, 1H),



carboxamide
3.79 (dd, J = 13.7, 7.7 Hz, 1H), 3.53 (dt, J = 7.4,




4.5 Hz, 2H), 3.43 (t, J = 5.2 Hz, 2H),




3.38 (s, 3H), 2.11 (td, J = 12.3, 7.2 Hz, 1H),




2.01-1.85 (m, 2H), 1.65 (dq, J = 12.2, 8.2 Hz,




1H)


156
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.78 (s, 1H), 8.22 (d, J = 2.1 Hz, 1H),
m/e



ylmethyl)-2-({[2-
8.03 (d, J = 2.1 Hz, 1H), 7.99 (dd, J = 9.3, 1.4 Hz,
487 (M + H)+



(propan-2-
1H), 7.96 (s, 1H), 7.91 (d, J = 9.3 Hz,



yloxy)ethyl]carbamoyl}[(2S)-
1H), 4.65 (s, 2H), 4.41 (dd, J = 15.4, 1.8 Hz,



tetrahydrofuran-2-
1H), 4.31-4.22 (m, 1H), 4.08 (dd, J = 15.4,



ylmethyl]amino)-
7.6 Hz, 1H), 3.96 (dd, J = 15.1, 7.0 Hz,



1,3-thiazole-5-
1H), 3.78 (dd, J = 14.0, 7.7 Hz, 1H),



carboxamide
3.65 (dt, J = 12.1, 6.1 Hz, 1H), 3.57 (t, J = 4.9 Hz,




2H), 3.41 (t, J = 5.3 Hz, 2H),




2.11 (td, J = 12.2, 7.1 Hz, 1H), 2.01-1.85 (m,




2H), 1.65 (dq, J = 12.3, 8.2 Hz, 1H),




1.17 (d, J = 6.1 Hz, 6H)


157
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(APCI(+))



a]pyridin-6-
8.78 (s, 1H), 8.21 (d, J = 2.0 Hz, 1H),
m/e



ylmethyl)-2-[{[2-
8.03 (d, J = 2.1 Hz, 1H), 7.99 (d, J = 11.6 Hz,
487 (M + H)+



(propan-2-
2H), 7.90 (d, J = 9.4 Hz, 1H), 4.65 (d, J = 3.9 Hz,



yloxy)ethyl]carbamoyl}(tetrahydrofuran-
2H), 4.24 (dd, J = 15.2, 7.6 Hz, 1H),



3-
4.12 (dd, J = 15.1, 8.0 Hz, 1H), 3.94 (td, J = 8.1,



ylmethyl)amino]-
5.7 Hz, 1H), 3.79-3.67 (m, 2H),



1,3-thiazole-5-
3.63 (dt, J = 8.2, 4.7 Hz, 2H), 3.57 (t, J = 5.8 Hz,



carboxamide
2H), 3.51-3.41 (m, 2H), 2.89-2.76 (m,




1H), 2.00 (td, J = 13.3, 7.9 Hz, 1H),




1.73 (dt, J = 20.3, 6.4 Hz, 1H), 1.15 (d, J = 6.1 Hz,




6H)









Example 116
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[2-oxo-4-(tetrahydrofuran-3-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide
Example 116A
2-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 2-bromothiazole-5-carboxylic acid for 4-nitrobenzoic acid.


Example 116B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[2-oxo-4-(tetrahydrofuran-3-yl)-1,3-oxazolidin-3-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 53B, substituting 4-(tetrahydrofuran-3-yl)oxazolidin-2-one for 4-cyanobenzylamine and 2-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)thiazole-5-carboxamide for 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide. 1H NMR (400 MHz, methanol-d4) δ 8.79 (s, 1H), 8.22 (d, J=1.9 Hz, 1H), 8.03 (s, 2H), 8.01-7.97 (m, 1H), 7.91 (d, J=9.5 Hz, 1H), 4.98-4.92 (m, 1H), 4.64 (dt, J=8.6, 4.5 Hz, 3H), 4.57-4.49 (m, 1H), 3.97 (td, J=8.5, 3.9 Hz, 1H), 3.81-3.71 (m, 1H), 3.71-3.59 (m, 2H), 2.26-2.02 (m, 1H), 1.96-1.85 (m, 1H), 1.78-1.65 (m, 1H); (APCI(+)) m/e 414 (M+H)+.


Table 9.


The following Examples were prepared essentially as described in Example 116, substituting the appropriate amine in Example 116A and the appropriate amine in Example 116B.















Ex
Name

1H NMR

MS







122
N-(imidazo[1,2-

(ESI(+))



a]pyridin-6-ylmethyl)-2-

m/e



(2-oxo-5-phenyl-1,3-

420 (M + H)+



oxazolidin-3-yl)-1,3-



thiazole-5-carboxamide


158
2-[5-(4-chlorophenyl)-

(ESI(+))



2-oxo-1,3-oxazolidin-3-

m/e



yl]-N-(imidazo[1,2-

454 (M + H)+



a]pyridin-6-ylmethyl)-



1,3-thiazole-5-



carboxamide


181
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



a]pyridin-7-ylmethyl)-2-
ppm 8.39 (d, J = 7.0 Hz, 1H), 8.04 (s,
m/e



[(4R)-2-oxo-4-(propan-
1H), 7.80 (s, 1H), 7.53 (s, 1H), 7.45 (s,
386 (M + H)+



2-yl)-1,3-oxazolidin-3-
1H), 6.97-6.87 (m, 1H), 4.75 (dt, J = 7.7,



yl]-1,3-thiazole-5-
3.8 Hz, 1H), 4.52 (dd, J = 9.5, 6.3 Hz,



carboxamide
2H), 2.85-2.65 (m, 1H), 0.99 (d, J = 7.1 Hz,




3H), 0.84 (d, J = 6.9 Hz, 3H)


185
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



a]pyridin-7-ylmethyl)-2-
ppm 9.26 (t, J = 5.5 Hz, 1H), 8.75 (d, J = 7.0 Hz,
m/e



[(4S)-2-oxo-4-(propan-
1H), 8.18 (d, J = 2.1 Hz, 1H),
386 (M + H)+



2-yl)-1,3-oxazolidin-3-
8.07 (s, 1H), 8.00 (d, J = 2.1 Hz, 1H),



yl]-1,3-thiazole-5-
7.81 (s, 1H), 7.48 (d, J = 7.0 Hz, 1H),



carboxamide
4.77 (dd, J = 7.7, 3.9 Hz, 1H), 4.55 (dd,




J = 10.7, 6.3 Hz, 2H), 2.76 (qd, J = 10.6,




7.1 Hz, 1H), 1.00 (d, J = 7.1 Hz,




3H), 0.84 (d, J = 6.9 Hz, 3H)


187
2-{(4R)-4-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



[(benzyloxy)methyl]-2-
ppm 8.40 (d, J = 7.0 Hz, 1H), 7.91 (s,
m/e



oxo-1,3-oxazolidin-3-
1H), 7.80 (s, 1H), 7.53 (s, 1H), 7.46 (s,
464 (M + H)+



yl}-N-(imidazo[1,2-
1H), 7.20 (ddd, J = 15.4, 11.1, 5.1 Hz,



a]pyridin-7-ylmethyl)-
5H), 6.93 (dd, J = 7.0, 1.3 Hz, 1H),



1,3-thiazole-5-
4.85 (dd, J = 6.1, 2.6 Hz, 1H),



carboxamide
4.67-4.52 (m, 5H), 4.41 (d, J = 12.2 Hz, 1H),




4.12 (dd, J = 10.2, 3.2 Hz, 1H), 3.63 (dd, J = 10.2,




1.6 Hz, 1H)


188
2-{(4S)-4-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



[(benzyloxy)methyl]-2-
ppm 8.35 (d, J = 7.0 Hz, 1H), 7.87 (s,
m/e



oxo-1,3-oxazolidin-3-
1H), 7.75 (s, 1H), 7.48 (s, 1H), 7.42 (s,
464 (M + H)+



yl}-N-(imidazo[1,2-
1H), 7.16 (ddd, J = 19.3, 11.3, 5.0 Hz,



a]pyridin-7-ylmethyl)-
5H), 6.88 (dd, J = 7.0, 1.3 Hz, 1H),



1,3-thiazole-5-
4.83-4.75 (m, 1H), 4.62-4.47 (m, 5H),



carboxamide
4.36 (d, J = 12.2 Hz, 1H), 4.07 (dd, J = 10.2,




3.2 Hz, 1H), 3.59 (dd, J = 10.2,




1.6 Hz, 1H)


218
2-{5-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



[(benzyloxy)methyl]-2-
ppm 8.39 (d, J = 7.0 Hz, 1H), 8.03 (s,
m/e



oxo-1,3-oxazolidin-3-
1H), 7.79 (s, 1H), 7.53 (s, 1H), 7.45 (s,
464 (M + H)+



yl}-N-(imidazo[1,2-
1H), 7.36-7.18 (m, 5H), 6.92 (d, J = 5.6 Hz,



a]pyridin-7-ylmethyl)-
1H), 5.02-4.99 (m, 2H),



1,3-thiazole-5-
4.59 (d, J = 2.3 Hz, 6H), 3.76 (ddd, J = 14.8,



carboxamide
11.2, 3.2 Hz, 1H)


244
2-[(2S)-2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



(hydroxymethyl)-5-
ppm 9.25 (t, J = 5.7 Hz, 1H), 8.75 (d, J = 7.0 Hz,
m/e



oxopyrrolidin-1-yl]-N-
1H), 8.18 (d, J = 1.9 Hz, 1H),
372 (M + H)+



(imidazo[1,2-a]pyridin-
8.10 (s, 1H), 8.00 (d, J = 2.1 Hz, 1H),



7-ylmethyl)-1,3-
7.81 (s, 1H), 7.48 (dd, J = 7.1, 1.3 Hz,



thiazole-5-carboxamide
1H), 4.75-4.69 (m, 3H), 4.17 (dd, J = 11.7,




3.4 Hz, 1H), 3.75 (dd, J = 11.7,




2.2 Hz, 1H), 2.88 (dt, J = 17.8, 10.1 Hz,




1H), 2.57 (ddd, J = 17.7, 10.1, 2.3 Hz,




1H), 2.48-2.33 (m, 1H),




2.33-2.18 (m, 1H)


245
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



a]pyridin-7-ylmethyl)-2-
ppm 8.75 (d, J = 7.0 Hz, 1H), 8.18 (d, J = 2.0 Hz,
m/e



[(4R)-4-methyl-2-oxo-
1H), 8.07 (s, 1H), 8.00 (t, J = 2.4 Hz,
358 (M + H)+



1,3-oxazolidin-3-yl]-
1H), 7.81 (s, 1H), 7.48 (dd, J = 7.0,



1,3-thiazole-5-
1.4 Hz, 1H), 4.87-4.78 (m, 1H),



carboxamide
4.73 (s, 2H), 4.69 (t, J = 8.5 Hz, 1H),




4.25 (dd, J = 8.7, 3.9 Hz, 1H), 1.57 (d, J = 6.3 Hz,




3H)


249
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



a]pyridin-7-ylmethyl)-2-
ppm 9.26 (t, J = 5.9 Hz, 1H), 8.75 (d, J = 7.0 Hz,
m/e



{2-oxo-5-[(propan-2-
1H), 8.18 (d, J = 2.0 Hz, 1H),
416 (M + H)+



yloxy)methyl]-1,3-
8.06 (s, 1H), 8.00 (d, J = 2.1 Hz, 1H),



oxazolidin-3-yl}-1,3-
7.81 (s, 1H), 7.48 (d, J = 7.0 Hz, 1H),



thiazole-5-carboxamide
4.98 (ddd, J = 9.1, 5.8, 2.9 Hz, 1H),




4.73 (s, 2H), 4.31 (t, J = 9.5 Hz, 1H),




4.14 (dd, J = 9.9, 5.6 Hz, 1H), 3.78 (dd,




J = 11.2, 2.9 Hz, 1H), 3.73-3.60 (m,




2H), 1.13 (d, J = 6.1 Hz, 6H)


251
2-[5-(hydroxymethyl)-

1H NMR (400 MHz, DMSO-d6) δ ppm

(APCI(+))



2-oxo-1,3-oxazolidin-3-
9.17 (t, J = 6.2 Hz, 1H), 8.50 (d, J = 6.9 Hz,
m/e



yl]-N-(imidazo[1,2-
1H), 8.14 (s, 1H), 7.90 (s, 1H),
374 (M + H)+



a]pyridin-7-ylmethyl)-
7.53 (s, 1H), 7.41 (s, 1H), 6.85 (d, J = 6.9 Hz,



1,3-thiazole-5-
1H), 5.29 (t, J = 5.6 Hz, 1H),



carboxamide
4.93-4.84 (m, 1H), 4.47 (d, J = 5.8 Hz, 2H),




4.24 (t, J = 9.4 Hz, 1H), 4.00 (dd, J = 9.8,




5.8 Hz, 1H), 3.76-3.66 (m, 1H),




3.66-3.56 (m, 1H)


255
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



a]pyridin-7-ylmethyl)-2-
8.40 (d, J = 7.0 Hz, 1H), 8.04 (s, 1H),
m/e



{(5S)-2-oxo-5-[(propan-
7.80 (s, 1H), 7.53 (s, 1H), 7.45 (s, 1H),
416 (M + H)+



2-yloxy)methyl]-1,3-
6.92 (d, J = 6.3 Hz, 1H), 5.01-4.94 (m,



oxazolidin-3-yl}-1,3-
1H), 4.59 (s, 2H), 4.31 (t, J = 9.5 Hz,



thiazole-5-carboxamide
1H), 4.13 (dd, J = 9.9, 5.6 Hz, 1H),




3.77 (dd, J = 11.2, 3.0 Hz, 1H),




3.72-3.58 (m, 2H), 1.13 (d, J = 6.1 Hz, 6H)


256
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ

(APCI(+))



a]pyridin-7-ylmethyl)-2-
ppm 8.40 (d, J = 7.0 Hz, 1H), 8.04 (s,
m/e



{(5R)-2-oxo-5-[(propan-
1H), 7.80 (s, 1H), 7.53 (s, 1H), 7.45 (s,
416 (M + H)+



2-yloxy)methyl]-1,3-
1H), 6.92 (d, J = 7.0 Hz, 1H),



oxazolidin-3-yl}-1,3-
5.03-4.95 (m, 1H), 4.59 (s, 2H), 4.31 (t, J = 9.5 Hz,



thiazole-5-carboxamide
1H), 4.13 (dd, J = 9.9, 5.7 Hz,




1H), 3.77 (dd, J = 11.2, 3.0 Hz, 1H),




3.71-3.58 (m, 2H), 1.13 (d, J = 6.1 Hz,




6H)









Example 117
4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.09 (s, 1H), 9.00-8.93 (m, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90-7.82 (m, 3H), 7.71-7.65 (m, 2H), 7.51 (d, J=1.2 Hz, 1H), 7.40-7.35 (m, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 2.37-2.31 (m, 2H), 2.31-2.16 (m, 1H), 1.81-1.68 (m, 2H), 1.67-1.44 (m, 4H), 1.26-1.10 (m, 2H); MS (ESI(+)) m/e 377 (M+H)+.


Example 118
2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide
Example 118A
2-cyclopentyl-N-(4-nitrophenyl)acetamide

The title compound was prepared as described in Example 1A, substituting 4-nitroaniline for 3-methylbutan-1-amine and 2-cyclopentylacetic acid for 4-nitrobenzoic acid.


Example 118B
N-(4-aminophenyl)-2-cyclopentylacetamide

The title compound was prepared as described in Example 1B, substituting 2-cyclopentyl-N-(4-nitrophenyl)acetamide for N-isopentyl-4-nitrobenzamide.


Example 118C
2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide

The title compound was prepared as described in Example 1C, substituting N-(4-aminophenyl)-2-cyclopentylacetamide for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (400 MHz, methanol-d4) δ ppm 8.76-8.69 (m, 1H), 8.16 (dd, J=2.2, 0.8 Hz, 1H), 7.98 (d, J=2.2 Hz, 1H), 7.81-7.77 (m, 1H), 7.49-7.41 (m, 3H), 7.36-7.30 (m, 2H), 4.59 (s, 2H), 2.37-2.24 (m, 3H), 1.90-1.77 (m, 2H), 1.75-1.52 (m, 4H), 1.32-1.18 (m, 2H); MS (ESI(+)) m/e 392 (M+H)+.


Example 119
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide

The title compound was prepared as described in Example 51A, substituting 4-bromo-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.18 (t, J=5.7 Hz, 1H), 8.75 (s, 1H), 8.28 (s, 2H), 8.02 (d, J=1.5 Hz, 1H), 7.97 (s, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.83-7.88 (m, 1H), 7.74-7.80 (m, 1H), 7.69 (d, J=8.3 Hz, 2H), 4.56 (d, J=5.7 Hz, 2H), 3.92 (d, J=7.2 Hz, 2H), 2.13 (dq, J=13.6, 6.8 Hz, 1H), 0.85 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 374 (M+H)+.


Example 137
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutanoyl)amino]-1,3-thiazole-5-carboxamide
Example 137A
2-(3-methylbutanamido)thiazole-5-carboxylic acid

The title compound was prepared as described in Example 52A, substituting 3-methylbutanoyl chloride for 2-cyclopentylacetyl chloride and methyl 2-aminothiazole-5-carboxylate for methyl 4-aminobenzoate.


Example 137B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-2-[(3-methylbutanoyl)amino]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 2-(3-methylbutanamido)thiazole-5-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6). δ ppm 12.31 (s, 1H), 9.05 (t, J=5.7 Hz, 1H), 8.54 (s, 1H), 7.97-8.11 (m, 2H), 7.56-7.71 (m, 2H), 7.34 (d, J=9.2 Hz, 1H), 4.44 (d, J=5.7 Hz, 2H), 2.33 (d, J=7.2 Hz, 2H), 2.07 (dq, J=13.6, 6.7, 6.6 Hz, 1H), 0.90 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 358 (M+H)+.


Example 159
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide
Example 159A
tert-butyl 4-(4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)benzoic acid for 4-nitrobenzoic acid.


Example 159B
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(piperidin-4-yloxy)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 159C
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(piperidin-4-yloxy)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.79-8.74 (m, 1H), 8.23-8.19 (m, 1H), 8.04-7.97 (m, 2H), 7.94-7.81 (m, 3H), 7.09-7.03 (m, 2H), 4.81-4.72 (m, 1H), 4.69 (s, 2H), 3.91-3.77 (m, 2H), 3.62-3.48 (m, 2H), 3.04-2.92 (m, 1H), 2.12-1.86 (m, 2H), 1.87-1.61 (m, 2H), 1.11 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 421 (M+H)+.


Table 10.


The following Examples were prepared essentially as described in Example 159, substituting the appropriate amine in Example 159A and the appropriate carboxylic acid in Example 159C.















Ex
Name

1H NMR

MS







160
4-[(1-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



acetylpiperidin-4-
8.80-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



yl)oxy]-N-
8.04-7.97 (m, 2H), 7.94-7.79 (m, 3H),
393 (M + H)+



(imidazo[1,2-
7.09-7.03 (m, 2H), 4.78-4.70 (m, 1H), 4.69 (s, 2H),



a]pyridin-6-
3.88-3.69 (m, 2H), 3.59-3.45 (m, 2H),



ylmethyl)benzamide
2.12 (s, 3H), 2.09-1.91 (m, 2H), 1.86-1.63 (m,




2H)


161
4-{[1-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



(cyclopropylcarbonyl)piperidin-
8.79-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



4-
8.04-7.97 (m, 2H), 7.93-7.82 (m, 3H),
419 (M + H)+



yl]oxy}-N-
7.10-7.04 (m, 2H), 4.81-4.73 (m, 1H), 4.69 (s, 2H),



(imidazo[1,2-
4.07-3.97 (m, 1H), 3.92-3.81 (m, 1H),



a]pyridin-6-
3.78-3.67 (m, 1H), 3.57-3.48 (m, 1H),



ylmethyl)benzamide
2.13-1.92 (m, 3H), 1.88-1.65 (m, 2H), 0.91-0.78 (m,




4H)


162
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.77 (m, 1H), 8.23-8.19 (m, 1H), 8.04-7.97 (m,
m/e



ylmethyl)-4-{[1-
2H), 7.94-7.82 (m, 3H), 7.09-7.03 (m, 2H),
463 (M + H)+



(tetrahydro-2H-
4.75 (m, 1H), 4.69 (s, 2H), 4.00-3.88 (m, 2H),



pyran-4-
3.89-3.80 (m, 2H), 3.63-3.45 (m, 4H),



ylcarbonyl)piperidin-
3.04-2.93 (m, 1H), 2.11-1.92 (m, 2H),



4-
1.86-1.65 (m, 4H), 1.66-1.58 (m, 2H)



yl]oxy}benzamide


163
4-{[1-(1,4-dioxan-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



2-
8.79-8.75 (m, 1H), 8.23-8.19 (m, 1H),
m/e



ylcarbonyl)piperidin-
8.04-7.97 (m, 2H), 7.93-7.82 (m, 3H), 7.09-7.02 (m,
465 (M + H)+



4-yl]oxy}-N-
2H), 4.79-4.71 (m, 1H), 4.69 (s, 2H),



(imidazo[1,2-
4.47-4.39 (m, 1H), 3.99-3.57 (m, 9H),



a]pyridin-6-
3.56-3.37 (m, 1H), 2.11-1.88 (m, 2H), 1.90-1.62 (m,



ylmethyl)benzamide
2H)


164
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.79-8.76 (m, 1H), 8.23-8.19 (m, 1H),
m/e



ylmethyl)-4-({1-
8.04-7.97 (m, 2H), 7.94-7.82 (m, 3H), 7.09-7.03 (m,
449 (M + H)+



[(2S)-
2H), 4.79-4.71 (m, 2H), 4.69 (s, 2H),



tetrahydrofuran-2-
3.98-3.72 (m, 4H), 3.66-3.43 (m, 2H),



ylcarbonyl]piperidin-
2.26-2.13 (m, 1H), 2.13-1.86 (m, 5H), 1.88-1.65 (m,



4-
2H)



yl}oxy)benzamide


165
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.79-8.75 (m, 1H), 8.23-8.19 (m, 1H),
m/e



ylmethyl)-4-({1-
8.04-7.97 (m, 2H), 7.93-7.82 (m, 3H), 7.09-7.03 (m,
449 (M + H)+



[(2R)-
2H), 4.79-4.71 (m, 1H), 4.69 (s, 1H),



tetrahydrofuran-2-
4.00-3.71 (m, 4H), 3.67-3.43 (m, 1H),



ylcarbonyl]piperidin-
2.26-2.13 (m, 1H), 2.13-1.86 (m, 5H), 1.88-1.65 (m,



4-
2H)



yl}oxy)benzamide


166
4-{[1-(2-hydroxy-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



2-
8.79-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



methylpropanoyl)piperidin-
8.04-7.97 (m, 2H), 7.93-7.81 (m, 3H),
437 (M + H)+



4-
7.08-7.02 (m, 2H), 4.78-4.70 (m, 1H), 4.69 (s, 2H),



yl]oxy}-N-
4.41-3.50 (m, 4H), 2.10-1.95 (m, 2H),



(imidazo[1,2-
1.82-1.69 (m, 2H), 1.44 (s, 6H)



a]pyridin-6-



ylmethyl)benzamide


167
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.79-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



ylmethyl)-4-({1-
8.04-7.97 (m, 2H), 7.93-7.82 (m, 3H),
451 (M + H)+



[(propan-2-
7.09-7.03 (m, 2H), 4.80-4.72 (m, 1H), 4.69 (s, 2H),



yloxy)acetyl]piperidin-
4.19 (s, 2H), 3.87-3.73 (m, 2H),



4-
3.73-3.62 (m, 1H), 3.59-3.45 (m, 2H), 2.11-1.93 (m,



yl}oxy)benzamide
2H), 1.87-1.68 (m, 2H), 1.19 (d, J = 6.1 Hz,




6H)


168
4-[(1-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



butanoylpiperidin-
8.79-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



4-yl)oxy]-N-
8.04-7.97 (m, 2H), 7.96-7.81 (m, 3H),
421 (M + H)+



(imidazo[1,2-
7.08-7.02 (m, 2H), 4.78-4.70 (m, 1H), 4.69 (s, 2H),



a]pyridin-6-
3.90-3.73 (m, 2H), 3.59-3.46 (m, 2H),



ylmethyl)benzamide
2.40 (t, J = 7.5 Hz, 2H), 2.10-1.90 (m, 2H),




1.84-1.57 (m, 4H), 0.98 (t, J = 7.4 Hz, 3H)


169
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.80-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



ylmethyl)-4-{[1-
8.04-7.97 (m, 2H), 7.94-7.82 (m, 3H),
451 (M + H)+



(3-methoxy-2-
7.09-7.03 (m, 2H), 4.80-4.71 (m, 1H), 4.69 (s, 2H),



methylpropanoyl)piperidin-
4.01-3.71 (m, 2H), 3.71-3.41 (m, 3H),



4-
3.38-3.31 (m, 1H), 3.30 (s, 3H), 3.26-3.16 (m, 1H),



yl]oxy}benzamide
2.12-1.88 (m, 2H), 1.87-1.61 (m, 2H),




1.06 (d, J = 6.8 Hz, 3H)


170
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.79-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



ylmethyl)-4-{[1-
8.04-7.97 (m, 2H), 7.94-7.81 (m, 3H),
461 (M + H)+



(3,3,3-
7.09-7.03 (m, 2H), 4.80-4.73 (m, 1H), 4.69 (s, 2H),



trifluoropropanoyl)piperidin-
3.90-3.72 (m, 2H), 3.66-3.47 (m, 4H),



4-
2.11-1.90 (m, 2H), 1.91-1.68 (m, 2H)



yl]oxy}benzamide


171
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.79-8.76 (m, 1H), 8.21 (dd, J = 2.1, 0.7 Hz, 1H),
m/e



ylmethyl)-4-{[1-
8.04-7.97 (m, 2H), 7.93-7.82 (m, 3H),
477 (M + H)+



(tetrahydro-2H-
7.09-7.03 (m, 2H), 4.78-4.71 (m, 1H), 4.68 (s, 2H),



pyran-4-
3.97-3.74 (m, 4H), 3.59-3.48 (m, 2H),



ylacetyl)piperidin-
3.48-3.38 (m, 2H), 2.37 (d, J = 7.0 Hz, 2H),



4-
2.10-1.90 (m, 3H), 1.85-1.60 (m, 4H),



yl]oxy}benzamide
1.41-1.26 (m, 2H)


172
4-{[1-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



(cyclopropylacetyl)piperidin-
8.79-8.75 (m, 1H), 8.21 (dd, J = 2.2, 0.7 Hz, 1H),
m/e



4-
8.04-7.97 (m, 2H), 7.93-7.82 (m, 3H),
433 (M + H)+



yl]oxy}-N-
7.09-7.03 (m, 2H), 4.79-4.71 (m, 1H), 4.69 (s, 2H),



(imidazo[1,2-
3.92-3.73 (m, 2H), 3.60-3.47 (m, 2H),



a]pyridin-6-
2.36 (d, J = 6.8 Hz, 2H), 2.10-1.91 (m, 2H),



ylmethyl)benzamide
1.86-1.65 (m, 2H), 1.08-0.94 (m, 1H),




0.58-0.47 (m, 2H), 0.23-0.16 (m, 2H)


173
N-(imidazo[1,2-

1H NMR (400 MHz, methanol-d4) δ ppm

(ESI(+))



a]pyridin-6-
8.80-8.75 (m, 1H), 8.22-8.19 (m, 1H),
m/e



ylmethyl)-4-{[1-
8.04-7.97 (m, 2H), 7.92-7.81 (m, 3H), 7.09-7.03 (m,
463 (M + H)+



(tetrahydrofuran-
2H), 4.79-4.70 (m, 1H), 4.69 (s, 2H),



2-
4.29-4.18 (m, 1H), 3.94-3.66 (m, 4H),



ylacetyl)piperidin-
3.65-3.45 (m, 2H), 2.76 (dd, J = 14.8, 7.6 Hz, 1H),



4-
2.52 (dd, J = 14.8, 5.2 Hz, 1H), 2.18-1.67 (m, 7H),



yl]oxy}benzamide
1.69-1.53 (m, 1H)


411
4-[(1-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



acetylpiperidin-4-
1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (m,
m/e



yl)oxy]-N-
3H), 7.51 (s, 1H), 7.37 (s, 1H), 7.07 (m, 2H),
393 (M + H)+



(imidazo[1,2-
6.85 (dd, J = 6.9, 1.6 Hz, 1H), 4.72 (m, 1H),



a]pyridin-7-
4.49 (d, J = 5.9 Hz, 2H), 3.85 (m, 1H), 3.68 (m,



ylmethyl)benzamide
1H), 3.50-3.15 (m, 2H), 2.02 (s, 3H),




2.03-1.85 (m 2H), 1.62 (m, 1H), 1.51 (m, 1H)


412
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylmethyl)-4-{[1-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
421 (M + H)+



(2-
1H), 7.07 (m, 2H), 6.85 (dd, J = 6.9, 1.7 Hz,



methylpropanoyl)piperidin-
1H), 4.73 (m, 1H), 4.49 (d, J = 5.9 Hz, 2H),



4-
3.96-3.70 (m, 2H), 3.45-3.20 (m, 2H),



yl]oxy}benzamide
2.89 (m, 1H), 1.93 (m, 2H), 1.58 (m, 2H), 1.00 (d, J = 6.7 Hz,




6H)


413
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylmethyl)-4-({1-
7.88 (m, 3H), 7.51 (s, 1H), 7.37 (s, 1H),
435 (M + H)+



[(2S)-2-
7.07 (m, 2H), 6.85 (dd, J = 6.9, 1.6 Hz, 1H), 4.74 (m,



methylbutanoyl]piperidin-
1H), 4.49 (d, J = 5.9 Hz, 2H), 4.00-3.74 (m,



4-
2H), 3.50-3.15 (m, 2H), 2.72 (m, 1H),



yl}oxy)benzamide
1.95 (m, 2H), 1.54 (m, 3H), 1.27 (m, 1H), 0.98 (d, J = 6.7 Hz,




3H), 0.81 (t, J = 7.4 Hz, 3H)


414
4-{[1-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.95 (t, J = 5.9 Hz,

(ESI(+))



(cyclopropylacetyl)piperidin-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



4-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
433 (M + H)+



yl]oxy}-N-
1H), 7.07 (m, 2H), 6.85 (dd, J = 7.0, 1.7 Hz,



(imidazo[1,2-
1H), 4.73 (m, 1H), 4.49 (d, J = 5.9 Hz, 2H),



a]pyridin-7-
3.89 (m, 1H), 3.69 (m, 1H), 3.40-3.15 (m,



ylmethyl)benzamide
2H), 2.28 (d, J = 6.7 Hz, 2H), 1.93 (m, 2H),




1.85-1.41 (m, 2H), 0.95 (m, 1H), 0.45 (m,




2H), 0.12 (m, 2H)


415
4-[(1-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



benzoylpiperidin-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



4-yl)oxy]-N-
7.90 (m, 3H), 7.51 (m, 1H), 7.47-7.37 (m,
455 (M + H)+



(imidazo[1,2-
5H), 7.36 (m, 1H), 7.07 (m, 2H), 6.84 (dd, J = 7.0,



a]pyridin-7-
1.7 Hz, 1H), 4.78 (m, 1H), 4.49 (d, J = 5.9 Hz,



ylmethyl)benzamide
2H), 4.00 (m, 1H), 3.55 (m, 1H),




3.45-3.15 (m, 2H), 2.00 (m, 2H), 164 (m, 2H)


416
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylmethyl)-4-({1-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
451 (M + H)+



[(propan-2-
1H), 7.07 (m, 2H), 6.85 (dd, J = 7.0, 1.7 Hz,



yloxy)acetyl]piperidin-
1H), 4.74 (m, 1H), 4.49 (d, J = 5.9 Hz, 2H),



4-
4.10 (d, J = 1.1 Hz, 2H), 3.85 (m, 1H), 3.70 (m,



yl}oxy)benzamide
1H), 3.60 (m, 1H), 3.40-3.15 (m, 2H),




1.97 (m, 2H), 1.69-1.45 (m, 2H), 1.11 (d, J = 6.1 Hz,




6H)


417
4-{[1-(2-hydroxy-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



2-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



methylpropanoyl)piperidin-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
437 (M + H)+



4-
1H), 7.07 (m, 2H), 6.85 (dd, J = 7.0, 1.7 Hz,



yl]oxy}-N-
1H), 5.42 (m, 1H), 4.73 (m, 1H), 4.49 (d, J = 5.9 Hz,



(imidazo[1,2-
2H), 4.42-3.78 (m, 2H),



a]pyridin-7-
3.70-3.20 (m, 2H), 1.95 (m, 2H), 1.57 (m, 2H), 1.32 (s,



ylmethyl)benzamide
6H)


418
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylmethyl)-4-({1-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
449 (M + H)+



[(2R)-
1H), 7.07 (m, 2H), 6.85 (dd, J = 7.0, 1.7 Hz,



tetrahydrofuran-2-
1H), 4.79-4.64 (m, 2H), 4.49 (d, J = 5.9 Hz,



ylcarbonyl]piperidin-
2H), 3.95-3.70 (m, 4H), 3.50-3.15 (m, 2H),



4-
2.10-1.90 (m, 4H), 1.90-1.75 (m, 2H),



yl}oxy)benzamide
1.70-1.43 (m, 2H)


419
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylmethyl)-4-({1-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
449 (M + H)+



[(2S)-
1H), 7.07 (m, 2H), 6.85 (dd, J = 6.9, 1.7 Hz,



tetrahydrofuran-2-
1H), 4.79-4.64 (m, 2H), 4.49 (d, J = 5.9 Hz,



ylcarbonyl]piperidin-
2H), 3.94-3.67 (m, 4H), 3.50-3.15 (m, 2H),



4-
2.10-1.90 (m, 4H), 1.90-1.75 (m, 2H),



yl}oxy)benzamide
1.70-1.43 (m, 2H)


420
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylmethyl)-4-{[1-
7.88 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
463 (M + H)+



(tetrahydro-2H-
1H), 7.07 (m, 2H), 6.85 (dd, J = 7.0, 1.7 Hz,



pyran-4-
1H), 4.73 (m, 1H), 4.49 (d, J = 5.9 Hz, 2H),



ylcarbonyl)piperidin-
3.84 (m, 4H), 3.45-3.15 (m, 4H), 2.90 (m,



4-
1H), 1.96 (m, 2H), 1.65-1.45 (m, 6H)



yl]oxy}benzamide


421
4-{[1-(1,4-dioxan-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 6.0 Hz,

(ESI(+))



2-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H),
m/e



ylcarbonyl)piperidin-
7.89 (m, 3H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (d,
465 (M + H)+



4-yl]oxy}-N-
J = 1.5 Hz, 1H), 7.07 (m, 2H), 6.85 (dd, J = 7.0,



(imidazo[1,2-
1.7 Hz, 1H), 4.74 (m, 1H), 4.49 (d, J = 5.9 Hz,



a]pyridin-7-
2H), 4.35 (dd, J = 9.4, 2.8 Hz, 1H),



ylmethyl)benzamide
3.90-3.55 (m, 7H), 3.55-3.15 (m, 3H), 1.98 (m, 2H),




1.75-1.40 (m, 2H)


422
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.95 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (d, J = 7.0 Hz, 1H), 7.89 (m,
m/e



ylmethyl)-4-{[1-
3H), 7.51 (s, 1H), 7.37 (bs, 1H), 7.07 (m, 2H),
477 (M + H)+



(tetrahydro-2H-
6.85 (dd, J = 6.9, 1.7 Hz, 1H), 4.72 (m, 1H),



pyran-4-
4.49 (d, J = 5.9 Hz, 2H), 3.95-3.67 (m, 4H),



ylacetyl)piperidin-
3.45-3.15 (m, 5H), 2.28 (m, 2H), 1.93 (m,



4-
2H), 1.67-1.42 (m, 4H), 1.26-1.12 (m, 2H)



yl]oxy}benzamide


423
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (t, J = 5.9 Hz,

(ESI(+))



a]pyridin-7-
1H), 8.48 (d, J = 7.0 Hz, 1H), 7.89 (m,
m/e



ylmethyl)-4-{[1-
3H), 7.51 (s, 1H), 7.37 (s, 1H), 7.07 (m, 2H),
478 (M + H)+



(morpholin-4-
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.73 (m, 1H),



ylacetyl)piperidin-
4.49 (d, J = 5.8 Hz, 2H), 3.86 (m, 2H), 3.57 (m,



4-
4H), 3.50-3.20 (m, 2H), 3.20-3.05 (m, 2H),



yl]oxy}benzamide
2.40 (m, 4H), 2.08-1.89 (m, 2H),




1.70-1.41 (m, 2H)









Example 204
2-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide
Example 204A
2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 2-bromothiazole-5-carboxylic acid for 4-nitrobenzoic acid.


Example 204B
2-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 51A, substituting 2-methyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrol-1-yl)propan-2-ol for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, methanol-d4) δ ppm 8.41 (d, J=7.05 Hz, 1H) 8.27 (d, J=7.92 Hz, 2H) 8.00 (s, 1H) 7.80 (s, 1H) 7.53 (s, 1H) 7.47 (s, 1H) 6.93 (dd, J=6.99, 1.36 Hz, 1H) 4.61 (s, 2H) 4.16 (s, 2H) 1.20 (s, 6H); MS (ESI)(+)) m/e 397 (M+H)+.


Example 205
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 51A, substituting 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, methanol-d4) δ ppm 8.40 (d, J=6.94 Hz, 1H) 8.27 (d, J=7.48 Hz, 2H) 8.00 (s, 1H) 7.80 (s, 1H) 7.53 (s, 1H) 7.47 (s, 1H) 6.93 (d, J=6.83 Hz, 1H) 4.61 (s, 2H) 4.01 (d, J=7.26 Hz, 2H) 2.12-2.30 (m, 1H) 0.93 (d, J=6.61 Hz, 6H); MS (ESI)(+)) m/e 381 (M+H)+.


Example 207
tert-butyl {4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(tert-butoxycarbonylamino)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.62 (s, 1H), 8.92 (t, J=6.0 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90-7.79 (m, 3H), 7.57-7.49 (m, 3H), 7.39-7.35 (m, 1H), 6.85 (dd, J=7.0, 1.6 Hz, 1H), 4.48 (d, J=5.8 Hz, 2H), 1.49 (s, 9H); MS (ESI(+)) m/e 367 (M+H)+.


Example 208
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide
Example 208A
tert-butyl {4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(tert-butoxycarbonylamino)benzoic acid for 4-nitrobenzoic acid.


Example 208B
4-amino-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl {4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 208C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]benzamide

The title compound was prepared as described in Example 1A, substituting 4-amino-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 3-methylbutan-1-amine and 2-(tetrahydro-2H-pyran-4-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.74 (dd, J=7.0, 0.9 Hz, 1H), 8.17 (dd, J=2.2, 0.7 Hz, 1H), 7.98 (d, J=2.2 Hz, 1H), 7.91-7.84 (m, 2H), 7.81-7.78 (m, 1H), 7.75-7.68 (m, 2H), 7.49 (dd, J=7.0, 1.6 Hz, 1H), 4.79-4.74 (m, 2H), 3.98-3.89 (m, 2H), 3.50-3.38 (m, 2H), 2.38-2.32 (m, 2H), 2.20-2.02 (m, 1H), 1.74-1.61 (m, 2H), 1.47-1.28 (m, 2H); MS (ESI(+)) m/e 393 (M+H)+.


Table 11.


The following Examples were prepared essentially as described in Example 208, substituting the appropriate carboxylic acid in Example 208A and the appropriate carboxylic acid in Example 208C.














Ex
Name
MS







209
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-2-
(ESI(+))



ylacetyl)amino]benzamide
m/e




379 (M + H)+


210
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[3-(tetrahydrofuran-2-
(ESI(+))



yl)propanoyl]amino}benzamide
m/e




393 (M + H)+


211
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(propan-2-
(ESI(+))



yloxy)acetyl]amino}benzamide
m/e




367 (M + H)+


212
4-[(3-cyclopentylpropanoyl)amino]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




391 (M + H)+


213
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(4-
(ESI(+))



methylpentanoyl)amino]benzamide
m/e




365 (M + H)+


214
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(tetrahydrofuran-3-
(ESI(+))



ylacetyl)amino]benzamide
m/e




379 (M + H)+


305
4-[(cyclopentylacetyl)amino]-3-fluoro-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




395 (M + H)+


463
4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




395 (M + H)+


867
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2-
(ESI(+))



methoxyphenyl)acetyl]amino}benzamide
m/e




415 (M + H)+


868
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-
(ESI(+))



[(phenylacetyl)amino]benzamide
m/e




385 (M + H)+


869
4-(benzoylamino)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
(ESI(+))




m/e




371 (M + H)+


870
2,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)carbamoyl]phenyl}benzamide
m/e




407 (M + H)+


871
3,5-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)carbamoyl]phenyl}benzamide
m/e




407 (M + H)+


872
3,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)carbamoyl]phenyl}benzamide
m/e




407 (M + H)+


873
2,4-difluoro-N-{4-[(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)carbamoyl]phenyl}benzamide
m/e




407 (M + H)+


874
2-fluoro-N-{4-[(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)carbamoyl]phenyl}benzamide
m/e




389 (M + H)+


875
N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-3-
(ESI(+))



methoxybenzamide
m/e




401 (M + H)+


876
4-{[(2-fluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




403 (M + H)+


880
N-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-2-
(ESI(+))



methoxybenzamide
m/e




401 (M + H)+


890
4-{[(2,5-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




421 (M + H)+


891
4-{[(2,4-difluorophenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




421 (M + H)+


895
4-{[difluoro(phenyl)acetyl]amino}-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




421 (M + H)+


896
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[(2-methyl-2-
(ESI(+))



phenylpropanoyl)amino]benzamide
m/e




413 (M + H)+









Example 215
4-[(4-cyanobenzyl)(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide
Example 215A
methyl 4-(4-cyanobenzylamino)benzoate

A solution of methyl 4-aminobenzoate (0.2 g, 1.323 mmol) and 4-formylbenzonitrile (0.177 g, 1.350 mmol) in methanol (2 ml) and dichloromethane (4 ml) was treated with acetic acid (0.379 ml, 6.62 mmol) followed by MP-cyanoborohydride (1.151 g, 2.65 mmol) and the reaction was slowly stirred at room temperature. After 16 hours, the mixture was filtered and concentrated and the concentrate was partitioned between 2 N sodium hydroxide and dichloromethane. The organic phase was concentrated to give the title compound with 30% of remaining 4-formylbenzonitrile.


Example 215B
methyl 4-(N-(4-cyanobenzyl)-2-cyclopentylacetamido)benzoate

The title compound was prepared as described in Example 52A, substituting methyl 4-(4-cyanobenzylamino)benzoate for methyl 4-aminobenzoate.


Example 215C
4-(N-(4-cyanobenzyl)-2-cyclopentylacetamido)benzoic acid

The title compound was prepared as described in Example 4B, substituting methyl 4-(N-(4-cyanobenzyl)-2-cyclopentylacetamido)benzoate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 215D
4-[(4-cyanobenzyl)(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(N-(4-cyanobenzyl)-2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.08 (t, J=5.8 Hz, 1H), 8.47 (s, 1H), 7.94 (s, 1H), 7.90-7.85 (m, 2H), 7.79-7.74 (m, 2H), 7.56-7.49 (m, 2H), 7.43-7.37 (m, 2H), 7.36-7.30 (m, 2H), 7.21 (dd, J=9.3, 1.7 Hz, 1H), 4.98 (bs, 2H), 4.45 (d, J=5.8 Hz, 2H), 2.19-2.13 (m, 3H), 1.74-1.66 (m, 2H), 1.51-1.38 (m, 4H), 1.01-0.92 (m, 2H); MS (ESI(+)) m/e 492 (M+H)+.


Example 216
tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (500 MHz, DMSO-d6) δ ppm 8.56 (s, 1H), 8.51-8.45 (m, 1H), 7.88 (s, 1H), 7.52-7.49 (m, 1H), 7.39-7.36 (m, 1H), 7.35-7.30 (m, 2H), 7.12-7.07 (m, 2H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.67 (t, J=6.0 Hz, 1H), 4.32 (d, J=6.0 Hz, 2H), 4.10-4.00 (m, 2H), 2.89-2.65 (m, 2H), 2.62-2.54 (m, 1H), 1.75-1.66 (m, 2H), 1.49-1.37 (m, 11H); MS (ESI(+)) m/e 450 (M+H)+.


Example 217
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.02 (t, J=6.0 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90-7.81 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.40-7.32 (m, 3H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.13-4.03 (m, 2H), 2.91-2.69 (m, 3H), 1.82-1.72 (m, 2H), 1.60-1.44 (m, 2H), 1.42 (s, 9H); MS (ESI(+)) m/e 435 (M+H)+.


Example 220
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}urea
Example 220A
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(piperidin-4-yl)phenyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 220B
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 1A, substituting 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(piperidin-4-yl)phenyl)urea for 3-methylbutan-1-amine and tetrahydrofuran-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.72 (d, J=7.0 Hz, 1H), 8.17-8.12 (m, 1H), 7.98-7.93 (m, 1H), 7.78 (bs, 1H), 7.48-7.41 (m, 1H), 7.35-7.28 (m, 2H), 7.18-7.12 (m, 2H), 4.81-4.72 (m, 1H), 4.67-4.55 (m, 3H), 4.19-4.08 (m, 1H), 4.01-3.91 (m, 1H), 3.90-3.81 (m, 1H), 3.24-3.09 (m, 1H), 2.85-2.67 (m, 2H), 2.30-2.14 (m, 1H), 2.09-1.79 (m, 5H), 1.73-1.46 (m, 2H); MS (ESI(+)) m/e 448 (M+H)+.


Table 12.


The following Examples were prepared essentially as described in Example 220, substituting the appropriate carboxylic acid in Example 220B.














Ex
Name
MS

















221
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-
(ESI(+))



4-ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




462 (M + H)+


222
1-{4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




464 (M + H)+


223
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-
(ESI(+))



4-ylacetyl)piperidin-4-yl]phenyl}urea
m/e




476 (M + H)+


224
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(morpholin-4-
(ESI(+))



ylacetyl)piperidin-4-yl]phenyl}urea
m/e




477 (M + H)+


225
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-
(ESI(+))



ylacetyl)piperidin-4-yl]phenyl}urea
m/e




462 (M + H)+


226
1-{4-[1-(3-hydroxy-3-methylbutanoyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




450 (M + H)+


227
1-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




436 (M + H)+


228
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-
(ESI(+))



methylpropanoyl)piperidin-4-yl]phenyl}urea
m/e




420 (M + H)+


229
1-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)urea
m/e




454 (M + H)+


243
1-(4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-
(ESI(+))



yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-
m/e



ylmethyl)urea
510 (M + H)+


286
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3S)-tetrahydrofuran-
(ESI(+))



3-ylcarbonyl]piperidin-4-yl}phenyl)urea
m/e




448 (M + H)+


287
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3R)-
(ESI(+))



tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)urea
m/e




448 (M + H)+


288
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-tetrahydrofuran-
(ESI(+))



2-ylcarbonyl]piperidin-4-yl}phenyl)urea
m/e




448 (M + H)+


289
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2R)-
(ESI(+))



tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)urea
m/e




448 (M + H)+


709
1-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)urea
m/e




420 (M + H)+


710
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2S)-2-
(ESI(+))



methylbutanoyl]piperidin-4-yl}phenyl)urea
m/e




434 (M + H)+


711
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-
(ESI(+))



methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




432 (M + H)+


712
1-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)urea
m/e




432 (M + H)+


713
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3,3,3-
(ESI(+))



trifluoropropanoyl)piperidin-4-yl]phenyl}urea
m/e




460 (M + H)+


714
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,4,4-
(ESI(+))



trifluorobutanoyl)piperidin-4-yl]phenyl}urea
m/e




474 (M + H)+


715
1-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




496 (M + H)+


716
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-
(ESI(+))



(phenylacetyl)piperidin-4-yl]phenyl}urea
m/e




468 (M + H)+


719
1-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)urea
m/e




472 (M + H)+


720
1-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)urea
m/e




472 (M + H)+


721
1-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)urea
m/e




472 (M + H)+


722
1-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




490 (M + H)+


723
1-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




490 (M + H)+


724
1-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




490 (M + H)+


725
1-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




490 (M + H)+


938
1-(4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




489 (M + H)+


939
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(3-methylbut-2-
ESI(+))



enoyl)piperidin-4-yl]phenyl}urea
m/e




432 (M + H)+


940
1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




448 (M + H)+


941
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methylcyclopent-
ESI(+))



1-en-1-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




458 (M + H)+


942
1-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)urea
m/e




448 (M + H)+


943
1-(4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




502 (M + H)+


944
1-{4-[1-(2,4-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




514 (M + H)+


945
1-{4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




458 (M + H)+


946
1-{4-[1-(2,5-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




514 (M + H)+


947
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-
ESI(+))



methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea
m/e




498 (M + H)+


948
1-{4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




498 (M + H)+


949
1-{4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




514 (M + H)+


950
1-{4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




477 (M + H)+


951
1-(4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




503 (M + H)+


952
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-
ESI(+))



methoxyphenyl)acetyl]piperidin-4-yl}phenyl)urea
m/e




498 (M + H)+


953
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-oxo-2,3-dihydro-
ESI(+))



1H-inden-4-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




508 (M + H)+


954
1-{4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




513 (M + H)+


955
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-2-methylbut-2-
ESI(+))



enoyl]piperidin-4-yl}phenyl)urea
m/e




432 (M + H)+


956
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(1H-indol-3-
ESI(+))



ylacetyl)piperidin-4-yl]phenyl}urea
m/e




507 (M + H)+


957
1-{4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




484 (M + H)+


1011
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(propan-2-yl)-1H-
ESI(+))



pyrazol-3-yl]carbonyl}piperidin-4-yl)phenyl]urea
m/e




486 (M + H)+


1012
1-(4-{1-[(2S)-2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl]piperidin-
ESI(+))



4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1013
1-(4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-
ESI(+))



yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-
m/e



ylmethyl)urea
497 (M + H)+


1014
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-4,5,6,7-
ESI(+))



tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




512 (M + H)+


1015
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-
ESI(+))



2,1-benzoxazol-3-ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




499 (M + H)+


1016
1-(4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




507 (M + H)+


1017
1-(4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




487 (M + H)+


1018
1-(4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




507 (M + H)+


1019
1-(4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




489 (M + H)+


1020
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[1-(pyridin-2-
ESI(+))



yl)cyclopropyl]carbonyl}piperidin-4-yl)phenyl]urea
m/e




495 (M + H)+


1021
1-(4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1022
1-[4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-
ESI(+))



yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




494 (M + H)+


1023
1-{4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-
ESI(+))



yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1024
1-{4-[1-(2,3-dihydro-1-benzofuran-2-ylcarbonyl)piperidin-4-
ESI(+))



yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




496 (M + H)+


1025
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-
ESI(+))



methoxycyclohexyl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




490 (M + H)+


1026
1-{4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-
ESI(+))



yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1027
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-4-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




505 (M + H)+


1028
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-1,3-
ESI(+))



benzoxazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




509 (M + H)+


1029
1-(4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-
ESI(+))



4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




514 (M + H)+


1030
1-(4-{1-[(1-cyanocyclopentyl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




471 (M + H)+


1031
1-{4-[1-(cinnolin-4-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




506 (M + H)+


1032
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinolin-7-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




505 (M + H)+


1033
1-{4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




497 (M + H)+


1034
1-(4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




485 (M + H)+


1035
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(5,6,7,8-
ESI(+))



tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




509 (M + H)+


1036
1-{4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-
m/e



ylmethyl)urea
511 (M + H)+


1037
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-7-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




505 (M + H)+


1038
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(quinoxalin-2-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




506 (M + H)+


1039
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(2-
ESI(+))



methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea
m/e




511 (M + H)+


1040
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2E)-3-(pyridin-2-
ESI(+))



yl)prop-2-enoyl]piperidin-4-yl}phenyl)urea
m/e




481 (M + H)+


1041
1-(4-{1-[(4-chloro-2,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e XXX




(M + H)+


1042
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(8-
ESI(+))



methylimidazo[1,2-a]pyridin-2-yl)carbonyl]piperidin-4-
m/e



yl}phenyl)urea
517 (M + H)+


1043
1-(4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




499 (M + H)+


4044
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-4,5,6,7-
ESI(+))



tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




512 (M + H)+


1045
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methyl-4H-
ESI(+))



furo[3,2-b]pyrrol-5-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




497 (M + H)+


1046
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2,3-
ESI(+))



dihydro-1-benzofuran-5-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




510 (M + H)+


1047
1-(4-{1-[(4-chloro-1-ethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




506 (M + H)+


1048
1-{4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




497 (M + H)+


1049
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(isoquinolin-8-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




505 (M + H)+


1050
1-(4-{1-[(4-cyanophenyl)acetyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




493 (M + H)+


1051
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(3-methoxythiophen-
ESI(+))



2-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




490 (M + H)+


1052
1-{4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




497 (M + H)+


1053
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(4,5,6,7-tetrahydro-
ESI(+))



1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




515 (M + H)+


1054
1-{4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




511 (M + H)+


1055
1-(4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




473 (M + H)+


1056
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[3-methyl-1-(prop-2-
ESI(+))



en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)phenyl]urea
m/e




498 (M + H)+


1057
1-{4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1058
1-(4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}phenyl)-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




489 (M + H)+


1059
1-(4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




483 (M + H)+


1060
1-{4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




511 (M + H)+


1065
1-(4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




517 (M + H)+


1066
1-(4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




492 (M + H)+


1121
1-(4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




501 (M + H)+


1122
1-{4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




511 (M + H)+


1123
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-
ESI(+))



indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




508 (M + H)+


1124
1-(4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-
ESI(+))



yl)carbonyl]piperidin-4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-
m/e



ylmethyl)urea
506 (M + H)+


1125
1-(4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




483 (M + H)+


1126
1-(4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




514 (M + H)+


1127
1-(4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




471 (M + H)+


1128
1-(4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




501 (M + H)+


1129
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(thieno[3,2-b]furan-5-
ESI(+))



ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




500 (M + H)+


1130
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxythiophen-
ESI(+))



2-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




490 (M + H)+


1131
1-(4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




485 (M + H)+


1132
1-(4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




495 (M + H)+


1133
1-{4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




515 (M + H)+


1134
1-[4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-
ESI(+))



yl]carbonyl}piperidin-4-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-
m/e



ylmethyl)urea
514 (M + H)+


1135
1-{4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




494 (M + H)+


1136
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(4-methoxy-5-
ESI(+))



methylpyridin-2-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




499 (M + H)+


1137
1-(4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1138
1-(4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}phenyl)-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




495 (M + H)+


1139
1-(4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




485 (M + H)+


1140
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[4-(propan-2-
ESI(+))



yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)phenyl]urea
m/e




498 (M + H)+


1141
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-5-propyl-
ESI(+))



1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




500 (M + H)+


1142
1-(4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




512 (M + H)+


1143
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(pyrazolo[1,5-
ESI(+))



a]pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}urea
m/e




494 (M + H)+


1144
1-{4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]phenyl}-3-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




494 (M + H)+


1145
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-(propan-2-yl)-1,3-
ESI(+))



oxazol-4-yl]carbonyl}piperidin-4-yl)phenyl]urea
m/e




487 (M + H)+


1146
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-
ESI(+))



indazol-7-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




508 (M + H)+


1147
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methoxy-5-
ESI(+))



methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




499 (M + H)+


1148
1-(4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-
ESI(+))



yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




515 (M + H)+


1149
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-
ESI(+))



indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




508 (M + H)+


1150
1-(4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}phenyl)-
ESI(+))



3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




517 (M + H)+


1151
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(2-methyl-2H-
ESI(+))



indazol-6-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




508 (M + H)+


1152
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{1-[(1-methyl-1H-
ESI(+))



indazol-4-yl)carbonyl]piperidin-4-yl}phenyl)urea
m/e




508 (M + H)+


1153
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-{[2-
ESI(+))



(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)phenyl]urea
m/e




512 (M + H)+









Example 230
4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
Example 230A
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 230B
4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 2-hydroxy-2-methylpropanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6/D2O, Temp=90° C.) δ ppm 8.77 (dd, J=6.9, 0.9 Hz, 1H), 8.22-8.18 (m, 1H), 8.02-7.98 (m, 1H), 7.88-7.81 (m, 2H), 7.77 (s, 1H), 7.44 (dd, J=6.9, 1.6 Hz, 1H), 7.40-7.34 (m, 2H), 4.76-4.64 (m, 4H), 2.98-2.82 (m, 3H), 1.89-1.81 (m, 2H), 1.65-1.48 (m, 2H), 1.38 (s, 6H); MS (ESI(+)) m/e 421 (M+H)+.


Table 13.


The following Examples were prepared essentially as described in Example 230, substituting the appropriate carboxylic acid in Example 230B.














Ex
Name
MS

















231
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-3-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




443 (M + H)+


232
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




447 (M + H)+


233
4-[1-(1,4-dioxan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




445 (M + H)+


234
4-{1-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]piperidin-
(ESI(+))



4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




495 (M + H)+


235
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydrofuran-2-
(ESI(+))



ylacetyl)piperidin-4-yl]benzamide
m/e




447 (M + H)+


236
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-2H-pyran-4-
(ESI(+))



ylacetyl)piperidin-4-yl]benzamide
m/e




461 (M + H)+


237
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(propan-2-
(ESI(+))



yloxy)acetyl]piperidin-4-yl}benzamide
m/e




435 (M + H)+


238
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-
(ESI(+))



methylbutanoyl]piperidin-4-yl}benzamide
m/e




419 (M + H)+


239
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
(ESI(+))



methylpropanoyl)piperidin-4-yl]benzamide
m/e




405 (M + H)+


308
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3S)-tetrahydrofuran-3-
(ESI(+))



ylcarbonyl]piperidin-4-yl}benzamide
m/e




433 (M + H)+


309
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3R)-tetrahydrofuran-3-
(ESI(+))



ylcarbonyl]piperidin-4-yl}benzamide
m/e




433 (M + H)+


310
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2R)-tetrahydrofuran-2-
(ESI(+))



ylcarbonyl]piperidin-4-yl}benzamide
m/e




433 (M + H)+


311
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-tetrahydrofuran-2-
(ESI(+))



ylcarbonyl]piperidin-4-yl}benzamide
m/e




433 (M + H)+


312
4-[1-(cyclopropylacetyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




417 (M + H)+


313
4-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




377 (M + H)+


437
4-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




439 (M + H)+


44
4-{1-[(3,3-difluorocyclobutyl)carbonyl]piperidin-4-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




453 (M + H)+


441
4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




481 (M + H)+


484
4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




429 (M + H)+


498
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-2-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




440 (M + H)+


499
4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




433 (M + H)+


500
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-
(ESI(+))



methylbenzoyl)piperidin-4-yl]benzamide
m/e




453 (M + H)+


501
4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




433 (M + H)+


502
4-[1-(cyclohexylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




445 (M + H)+


503
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-2-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




445 (M + H)+


504
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3,3,3-
(ESI(+))



trifluoropropanoyl)piperidin-4-yl]benzamide
m/e




445 (M + H)+


505
4-(1-butanoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




405 (M + H)+


506
4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




475 (M + H)+


507
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
(ESI(+))



methylbenzoyl)piperidin-4-yl]benzamide
m/e




453 (M + H)+


508
4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




457 (M + H)+


509
4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




419 (M + H)+


510
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylpent-2-
(ESI(+))



enoyl]piperidin-4-yl}benzamide
m/e




431 (M + H)+


511
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-
(ESI(+))



5-yl)carbonyl]piperidin-4-yl}benzamide
m/e




443 (M + H)+


512
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methyloxetan-3-
(ESI(+))



yl)carbonyl]piperidin-4-yl}benzamide
m/e




433 (M + H)+


513
4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




457 (M + H)+


514
4-{1-[(1-cyanocyclopropyl)carbonyl]piperidin-4-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




428 (M + H)+


515
4-[1-(cyclopentylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




431 (M + H)+


516
4-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




457 (M + H)+


517
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrazol-
(ESI(+))



4-yl)carbonyl]piperidin-4-yl}benzamide
m/e




443 (M + H)+


518
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
(ESI(+))



oxobutanoyl)piperidin-4-yl]benzamide
m/e




419 (M + H)+


519
4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




457 (M + H)+


520
4-[1-(4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




464 (M + H)+


521
4-[1-(3-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




464 (M + H)+


522
4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




475 (M + H)+


523
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-2-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




441 (M + H)+


524
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methylthiophen-2-
(ESI(+))



yl)carbonyl]piperidin-4-yl}benzamide
m/e




459 (M + H)+


525
4-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]piperidin-4-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




458 (M + H)+


526
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
(ESI(+))



methoxybenzoyl)piperidin-4-yl]benzamide
m/e




469 (M + H)+


527
4-[1-(3-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




473 (M + H)+


528
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-
(ESI(+))



methoxybenzoyl)piperidin-4-yl]benzamide
m/e




469 (M + H)+


529
4-[1-(4-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




473 (M + H)+


530
4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




475 (M + H)+


531
4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




403 (M + H)+


532
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-propanoylpiperidin-4-
(ESI(+))



yl)benzamide
m/e




391 (M + H)+


533
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-pyrrol-2-
(ESI(+))



yl)carbonyl]piperidin-4-yl}benzamide
m/e




442 (M + H)+


534
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
(ESI(+))



methylbutanoyl)piperidin-4-yl]benzamide
m/e




419 (M + H)+


535
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-4-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




440 (M + H)+


536
4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




433 (M + H)+


537
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyridin-3-
(ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




440 (M + H)+


538
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-
(ESI(+))



methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide
m/e




417 (M + H)+


539
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
(ESI(+))



methoxybenzoyl)piperidin-4-yl]benzamide
m/e




469 (M + H)+


699
4-[1-(2-chlorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




473 (M + H)+


700
4-[1-(2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




475 (M + H)+


701
4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




475 (M + H)+


702
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-
(ESI(+))



(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide
m/e




507 (M + H)+


703
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-
(ESI(+))



(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide
m/e




523 (M + H)+


704
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-
(ESI(+))



(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide
m/e




523 (M + H)+


705
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[4-
(ESI(+))



(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide
m/e




507 (M + H)+


706
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-
(ESI(+))



(trifluoromethoxy)benzoyl]piperidin-4-yl}benzamide
m/e




523 (M + H)+


707
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylacetyl)piperidin-
(ESI(+))



4-yl]benzamide
m/e




453 (M + H)+


708
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-
(ESI(+))



(trifluoromethyl)benzoyl]piperidin-4-yl}benzamide
m/e




507 (M + H)+


737
4-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)benzamide
m/e




464 (M + H)+


913
4-{1-[(2-chloropyridin-3-yl)carbonyl]piperidin-4-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




474 (M + H)+


914
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-methylbut-2-
ESI(+))



enoyl)piperidin-4-yl]benzamide
m/e




417 (M + H)+


915
4-[1-(3-fluoro-4-methoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




487 (M + H)+


916
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methylcyclopent-1-
ESI(+))



en-1-yl)carbonyl]piperidin-4-yl}benzamide
m/e




443 (M + H)+


917
4-[1-(2-ethylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
ESI(+))



ylmethyl)benzamide
m/e




433 (M + H)+


918
4-{1-[(4-fluorophenoxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




487 (M + H)+


919
4-[1-(3,5-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




499 (M + H)+


920
4-[1-(cyclohex-3-en-1-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




443 (M + H)+


921
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-
ESI(+))



methoxyphenyl)acetyl]piperidin-4-yl}benzamide
m/e




483 (M + H)+


922
4-[1-(3-hydroxy-2-phenylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




483 (M + H)+


923
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
ESI(+))



methylbenzoyl)piperidin-4-yl]benzamide
m/e




453 (M + H)+


924
4-[1-(2-acetylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-
ESI(+))



ylmethyl)benzamide
m/e




481 (M + H)+


925
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[2-
ESI(+))



(methoxymethyl)benzoyl]piperidin-4-yl}benzamide
m/e




483 (M + H)+


926
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
ESI(+))



phenylpropanoyl)piperidin-4-yl]benzamide
m/e




467 (M + H)+


927
4-[1-(2,6-dimethoxybenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




499 (M + H)+


928
4-[1-(N,N-diethyl-beta-alanyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




462 (M + H)+


929
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[(2-
ESI(+))



methylpropyl)sulfonyl]acetyl}piperidin-4-yl)benzamide
m/e




497 (M + H)+


930
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
ESI(+))



phenoxypropanoyl)piperidin-4-yl]benzamide
m/e




483 (M + H)+


931
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-({[(1R,2S)-2-
ESI(+))



methylcyclohexyl]oxy}acetyl)piperidin-4-yl]benzamide
m/e




489 (M + H)+


932
4-{1-[(2-chloro-6-methylpyridin-4-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




488 (M + H)+


933
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-
ESI(+))



methoxyphenyl)acetyl]piperidin-4-yl}benzamide
m/e




483 (M + H)+


934
4-[1-(2-chloro-4-cyanobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




498 (M + H)+


935
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-2-methylbut-2-
ESI(+))



enoyl]piperidin-4-yl}benzamide
m/e




417 (M + H)+


936
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-
ESI(+))



methylphenyl)acetyl]piperidin-4-yl}benzamide
m/e




497 (M + H)+


937
4-[1-(2-hydroxy-3-methylbenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




469 (M + H)+


959
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-
ESI(+))



pyrazol-3-yl]carbonyl}piperidin-4-yl)benzamide
m/e




471 (M + H)+


960
4-{1-[(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-
ESI(+))



4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




483 (M + H)+


961
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-4,5,6,7-
ESI(+))



tetrahydro-2H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide
m/e




497 (M + H)+


962
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-2,1-
ESI(+))



benzoxazol-3-ylcarbonyl)piperidin-4-yl]benzamide
m/e




484 (M + H)+


963
4-{1-[(3-fluoro-6-methylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




472 (M + H)+


964
4-{1-[(2-chloro-3-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




492 (M + H)+


965
4-{1-[(3-chloropyridin-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




474 (M + H)+


966
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(pyridin-2-
ESI(+))



yl)cyclopropyl]carbonyl}piperidin-4-yl)benzamide
m/e




480 (M + H)+


967
4-{1-[(1-cyclopentyl-1H-pyrazol-3-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




497 (M + H)+


968
4-{1-[2-(3-fluorophenoxy)propanoyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




501 (M + H)+


969
4-(1-{[1-(difluoromethyl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-
ESI(+))



yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




479 (M + H)+


970
4-[1-(3,4-dihydro-2H-chromen-6-ylcarbonyl)piperidin-4-yl]-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




495 (M + H)+


971
4-{1-[(cyclohexyloxy)acetyl]piperidin-4-yl}-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




475 (M + H)+


972
4-{1-[(2-chloropyridin-3-yl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




488 (M + H)+


973
4-{1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




470 (M + H)+


974
4-[1-(2H-chromen-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




493 (M + H)+


975
4-{1-[(3,5-difluoropyridin-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




476 (M + H)+


976
4-[1-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperidin-4-yl]-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




497 (M + H)+


977
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-
ESI(+))



methoxycyclohexyl)carbonyl]piperidin-4-yl}benzamide
m/e




475 (M + H)+


978
4-[1-(2,3-dihydro-1,4-benzodioxin-5-ylcarbonyl)piperidin-4-yl]-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




497 (M + H)+


979
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-4-
ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




490 (M + H)+


980
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-1,3-
ESI(+))



benzoxazol-6-yl)carbonyl]piperidin-4-yl}benzamide
m/e




494 (M + H)+


981
4-{1-[(1-tert-butyl-3-methyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-
ESI(+))



yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




499 (M + H)+


982
4-{1-[(1-cyanocyclopentyl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




456 (M + H)+


983
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thieno[3,2-b]pyridin-2-
ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




496 (M + H)+


984
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinolin-7-
ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




490 (M + H)+


985
4-[1-(5-cyano-2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




482 (M + H)+


986
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(5,6,7,8-
ESI(+))



tetrahydroquinolin-3-ylcarbonyl)piperidin-4-yl]benzamide
m/e




494 (M + H)+


987
4-[1-(3,4-dihydro-2H-pyrano[2,3-b]pyridin-6-ylcarbonyl)piperidin-
ESI(+))



4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




496 (M + H)+


988
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-7-
ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




490 (M + H)+


989
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(quinoxalin-2-
ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




491 (M + H)+


990
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(2-
ESI(+))



methoxypyridin-3-yl)prop-2-enoyl]piperidin-4-yl}benzamide
m/e




496 (M + H)+


991
-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2E)-3-(pyridin-2-
ESI(+))



yl)prop-2-enoyl]piperidin-4-yl}benzamide
m/e




466 (M + H)+


992
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(8-methylimidazo[1,2-
ESI(+))



a]pyridin-2-yl)carbonyl]piperidin-4-yl}benzamide
m/e




493 (M + H)+


993
4-{1-[(2-ethoxypyridin-4-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




484 (M + H)+


994
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-4,5,6,7-
ESI(+))



tetrahydro-1H-indazol-3-yl)carbonyl]piperidin-4-yl}benzamide
m/e




497 (M + H)+


995
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methyl-4H-furo[3,2-
ESI(+))



b]pyrrol-5-yl)carbonyl]piperidin-4-yl}benzamide
m/e




482 (M + H)+


996
4-[1-(3-cyano-5-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




482 (M + H)+


997
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(isoquinolin-8-
ESI(+))



ylcarbonyl)piperidin-4-yl]benzamide
m/e




490 (M + H)+


998
4-{1-[(4-cyanophenyl)acetyl]piperidin-4-yl}-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




478 (M + H)+


999
4-[1-(3-cyano-4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




482 (M + H)+


1000
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4,5,6,7-tetrahydro-1,3-
ESI(+))



benzothiazol-2-ylcarbonyl)piperidin-4-yl]benzamide
m/e




500 (M + H)+


1001
4-[1-(1,3-benzothiazol-2-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




496 (M + H)+


1002
4-{1-[(3-ethyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




458 (M + H)+


1003
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[3-methyl-1-(prop-2-
ESI(+))



en-1-yl)-1H-pyrazol-5-yl]carbonyl}piperidin-4-yl)benzamide
m/e




483 (M + H)+


1004
4-[1-(1,2,3-benzothiadiazol-5-ylcarbonyl)piperidin-4-yl]-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




497 (M + H)+


1005
4-{1-[(2-ethyl-1,3-thiazol-4-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




474 (M + H)+


1006
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-
ESI(+))



yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)benzamide
m/e




483 (M + H)+


1007
4-{1-[(5,6-dimethylpyridin-3-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




468 (M + H)+


1008
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-
ESI(+))



yl)tetrahydro-2H-pyran-4-yl]carbonyl}piperidin-4-yl)benzamide
m/e




489 (M + H)+


1009
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methoxy-6-
ESI(+))



methylbenzoyl)piperidin-4-yl]benzamide
m/e




483 (M + H)+


1010
4-[1-(1,3-benzothiazol-7-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




496 (M + H)+


1061
4-{1-[(2-chloro-5-fluoropyridin-4-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




493 (M + H)+


1062
4-{1-[(3-cyclopropyl-1,2-oxazol-5-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




471 (M + H)+


1063
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-methoxythiophen-2-
ESI(+))



yl)carbonyl]piperidin-4-yl}benzamide
m/e




476 (M + H)+


1064
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-methyl-5-(propan-2-
ESI(+))



yl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide
m/e




486 (M + H)+


1084
4-{1-[(2-cyclopropyl-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




486 (M + H)+


1085
4-[1-(1,3-benzothiazol-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




496 (M + H)+


1086
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-
ESI(+))



6-yl)carbonyl]piperidin-4-yl}benzamide
m/e




493 (M + H)+


1087
4-{1-[(4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-
ESI(+))



yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




491 (M + H)+


1088
4-{1-[(5-ethylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




468 (M + H)+


1089
4-{1-[(3-chloro-5-cyanopyridin-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




499 (M + H)+


1090
4-{1-[(1-cyano-3-methylcyclobutyl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




456 (M + H)+


1091
4-{1-[(1,5-diethyl-1H-1,2,3-triazol-4-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




486 (M + H)+


1092
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxythiophen-2-
ESI(+))



yl)carbonyl]piperidin-4-yl}benzamide
m/e




475 (M + H)+


1093
4-{1-[(5-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




470 (M + H)+


1094
4-{1-[(5-cyclopropylpyridin-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




480 (M + H)+


1095
4-[1-(4-cyano-2,6-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




500 (M + H)+


1096
4-(1-{[1-ethyl-3-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidin-
ESI(+))



4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




499 (M + H)+


1097
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[1-(propan-2-yl)-1H-
ESI(+))



pyrazol-3-yl]acetyl}piperidin-4-yl)benzamide
m/e




485 (M + H)+


1098
4-[1-(1-benzofuran-3-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




479 (M + H)+


1099
Example 1099
ESI(+))



N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(3-meth-5,6,7,8-
m/e



tetrahydroimidazo[1,5-a]pyridin-1-yl)carbonyl]piperidin-4-
497 (M + H)+



yl}benzamide


1100
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(4-methoxy-5-
ESI(+))



methylpyridin-2-yl)carbonyl]piperidin-4-yl}benzamide
m/e




484 (M + H)+


1101
4-{1-[(1-cyclopentyl-1H-pyrazol-5-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




497 (M + H)+


1102
4-{1-[(4-chloro-1,3-thiazol-5-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




480 (M + H)+


1103
4-{1-[(3-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




470 (M + H)+


1104
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[4-(propan-2-
ESI(+))



yl)pyrimidin-5-yl]carbonyl}piperidin-4-yl)benzamide
m/e




483 (M + H)+


1105
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-5-propyl-
ESI(+))



1H-pyrazol-4-yl)carbonyl]piperidin-4-yl}benzamide
m/e




485 (M + H)+


1106
4-{1-[2-(3-cyclopropyl-1H-pyrazol-1-yl)propanoyl]piperidin-4-yl}-
ESI(+))



N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




497 (M + H)+


1107
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2,3-dihydro-
ESI(+))



1-benzofuran-7-yl)carbonyl]piperidin-4-yl}benzamide
m/e




495 (M + H)+


1108
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)-1,3-
ESI(+))



thiazol-4-yl]carbonyl}piperidin-4-yl)benzamide
m/e




488 (M + H)+


1109
4-(1-{[1-(difluoromethyl)-5-methyl-1H-pyrazol-3-
ESI(+))



yl]carbonyl}piperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-
m/e



ylmethyl)benzamide
493 (M + H)+


1110
4-{1-[(4-cyanothiophen-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




470 (M + H)+


1111
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazolo[1,5-a]pyridin-
ESI(+))



2-ylcarbonyl)piperidin-4-yl]benzamide
m/e




479 (M + H)+


1112
4-[1-(1-benzofuran-5-ylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




479 (M + H)+


1113
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-(propan-2-yl)-1,3-
ESI(+))



oxazol-4-yl]carbonyl}piperidin-4-yl)benzamide
m/e




472 (M + H)+


1114
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methoxy-5-
ESI(+))



methylpyridin-3-yl)carbonyl]piperidin-4-yl}benzamide
m/e




484 (M + H)+


1115
4-{1-[(5,6-dimethoxypyridin-2-yl)carbonyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




500 (M + H)+


1116
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-
ESI(+))



4-yl)carbonyl]piperidin-4-yl}benzamide
m/e




493 (M + H)+


1117
4-{1-[(2-ethylpiperidin-1-yl)(oxo)acetyl]piperidin-4-yl}-N-
ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




502 (M + H)+


1118
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-methyl-2H-indazol-
ESI(+))



6-yl)carbonyl]piperidin-4-yl}benzamide
m/e




493 (M + H)+


1119
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-methyl-1H-indazol-
ESI(+))



4-yl)carbonyl]piperidin-4-yl}benzamide
m/e




493 (M + H)+


1120
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-{[2-
ESI(+))



(trifluoromethyl)furan-3-yl]carbonyl}piperidin-4-yl)benzamide
m/e




497 (M + H)+









Example 240
4-[(4-cyanobenzyl)(3-methoxypropanoyl)amino]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 215, substituting 3-methoxypropanoyl chloride for 2-cyclopentylacetyl chloride in Example 215B. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.08 (t, J=5.8 Hz, 1H), 8.46 (dd, J=1.9, 0.9 Hz, 1H), 7.94 (dd, J=1.2, 0.6 Hz, 1H), 7.91-7.85 (m, 2H), 7.79-7.73 (m, 2H), 7.56-7.49 (m, 2H), 7.43-7.39 (m, 2H), 7.38-7.33 (m, 2H), 7.20 (dd, J=9.2, 1.7 Hz, 1H), 5.00 (bs, 2H), 4.45 (d, J=5.8 Hz, 2H), 3.54 (t, J=6.2 Hz, 2H), 3.17 (s, 3H), 2.43-2.35 (m, 2H); MS (ESI(+)) m/e 468 (M+H)+.


Example 241
5-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 241A
5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

A solution of 5-bromothiophene-2-carboxylic acid (1.279 g, 6.18 mmol), imidazo[1,2-a]pyridin-7-ylmethanamine (1 g, 6.79 mmol), 1-hydroxybenzotriazole hydrate (1.041 g, 6.79 mmol) and N-methylmorpholine (1.698 ml, 15.44 mmol) in dimethylformamide (20 ml) at room temperature was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.131 g, 11.12 mmol). The mixture was stirred overnight and poured into a gently stirred round-bottom flask containing water (100 ml) and ethyl acetate (30 ml). The resulting bilayer suspension was stirred for several minutes, filtered and washed with water then minimal ethyl acetate to give the title compound after drying.


Example 241B
tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline.


Example 241C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 241D
5-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting acetyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.13-9.06 (m, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.72 (d, J=3.9 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.38 (s, 1H), 7.15 (t, J=4.2 Hz, 1H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.28-6.21 (m, 1H), 4.46 (d, J=5.9 Hz, 2H), 4.15-4.04 (m, 2H), 3.61 (dt, J=11.3, 5.6 Hz, 2H), 2.63-2.35 (m, 2H), 2.07-1.99 (m, 3H); MS (ESI)(+)) m/e 381 (M+H)+.


Example 242
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting methanesulfonyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.15-9.07 (m, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.73 (d, J=3.9 Hz, 1H), 7.51 (s, 1H), 7.38 (bs, 1H), 7.17 (d, J=3.9 Hz, 1H), 6.83 (d, J=7.0 Hz, 1H), 6.28 (bs, 1H), 4.49-4.43 (m, 2H), 3.88-3.82 (m, 2H), 3.29-3.07 (m, 2H), 2.93 (s, 3H), 2.65-2.41 (m, 2H); MS (ESI)(+)) m/e 417 (M+H)+.


Example 246
5-[1-(cyclopropylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting cyclopropyl sulfonyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.10 (t, J=6.0 Hz, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.73 (d, J=3.9 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.38 (s, 1H), 7.17 (d, J=3.9 Hz, 1H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.28 (bs, 1H), 4.46 (d, J=5.9 Hz, 2H), 3.95-3.89 (m, 2H), 3.43 (t, J=5.7 Hz, 2H), 2.73-2.56 (m, 3H), 1.26-0.89 (m, 4H); MS (ESI)(+)) m/e 443 (M+H)+.


Example 250
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[(4R)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl]thiophene-2-carboxamide

A solution of 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide (84 mg, 0.25 mmol), (R)-4-isopropyloxazolidin-2-one (32 mg, 0.25 mmol), N,N-dimethylethane-1,2-diamine (2 mg, 0.025 mmol), copper(I) iodide (5 mg, 0.025 mmol) and potassium carbonate (121 mg, 0.88 mmol) in dioxane (1 ml) was stirred at 110° C. overnight. Concentration and reverse phase chromatography provided the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.13 (t, J=5.3 Hz, 1H), 8.74 (d, J=5.5 Hz, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 7.79 (s, 1H), 7.62 (d, J=4.1 Hz, 1H), 7.47 (d, J=7.0 Hz, 1H), 6.77 (d, J=4.2 Hz, 1H), 4.72 (s, 2H), 4.61-4.42 (m, 3H), 2.46 (ddd, J=10.2, 6.9, 3.5 Hz, 1H), 1.00 (d, J=7.0 Hz, 3H), 0.85 (d, J=6.8 Hz, 3H); (APCI(+)) m/e 385 (M+H)+.


Example 257
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methoxyacetyl)piperidin-4-yl]thiophene-2-carboxamide
Example 257A
tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 257B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 257C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methoxyacetyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and methoxyacetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.39 (d, J=7.0 Hz, 1H), 7.79 (s, 1H), 7.60 (d, J=3.8 Hz, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.44 (s, 1H), 6.96 (d, J=3.8 Hz, 1H), 6.92 (dd, J=7.1, 1.2 Hz, 1H), 4.58 (bs, 2H), 3.85-3.76 (m, 2H), 3.03 (tt, J=11.8, 3.8 Hz, 1H), 2.97-2.82 (m, 5H), 2.18-2.09 (m, 2H), 1.96 (s, 1H), 1.86-1.71 (m, 2H); MS (ESI(+)) m/e 413 (M+H)+.


Table 14.


The following Examples were prepared essentially as described in Example 257, substituting the appropriate carboxylic acid in Example 257C.














Ex
Name
MS







258
5-(1-acetylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)thiophene-2-carboxamide
m/e




383 (M + H)+


259
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-
(ESI(+))



methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide
m/e




411 (M + H)+


260
5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e




409 (M + H)+


261
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydrofuran-3-
(ESI(+))



ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide
m/e




439 (M + H)+


262
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-
(ESI(+))



ylacetyl)piperidin-4-yl]thiophene-2-carboxamide
m/e




467 (M + H)+


263
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-
(ESI(+))



methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide
m/e




425 (M + H)+


264
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(1,2-oxazol-5-
(ESI(+))



ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide
m/e




436 (M + H)+


879
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-methyl-2-(piperazin-
(ESI(+))



1-yl)propanoyl]piperidin-4-yl}thiophene-2-carboxamide
m/e




495 (M + H)+


887
5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)thiophene-2-carboxamide
m/e




481 (M + H)+


888
5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)thiophene-2-carboxamide
m/e




481 (M + H)+









Example 266
5-[5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 250, substituting 5-(hydroxymethyl)oxazolidin-2-one for (R)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, methanol-d4) δ ppm 9.10 (s, 1H), 8.74 (d, J=7.0 Hz, 1H), 8.17 (d, J=2.0 Hz, 1H), 7.98 (d, J=2.1 Hz, 1H), 7.78 (s, 1H), 7.60 (d, J=4.2 Hz, 1H), 7.52-7.41 (m, 1H), 6.60 (d, J=4.2 Hz, 1H), 4.84 (s, 1H), 4.71 (d, J=4.2 Hz, 2H), 4.16 (t, J=9.1 Hz, 1H), 3.98 (dd, J=8.9, 6.2 Hz, 1H), 3.88 (dd, J=12.7, 3.0 Hz, 1H), 3.69 (dd, J=12.7, 3.6 Hz, 1H); (APCI(+)) m/e 373 (M+H)+.


Example 267
5-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 250, substituting (R)-5-hydroxyoxazolidin-2-one for (R)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, methanol-d4) δ ppm 9.10 (t, J=6.1 Hz, 1H), 8.73 (d, J=6.9 Hz, 1H), 8.16 (d, J=1.8 Hz, 1H), 7.98 (d, J=2.0 Hz, 1H), 7.78 (s, 1H), 7.61 (d, J=4.2 Hz, 1H), 7.46 (d, J=7.7 Hz, 1H), 6.68 (d, J=4.2 Hz, 1H), 4.71 (s, 2H), 4.62 (t, J=5.7 Hz, 1H), 4.15 (dd, J=10.9, 5.3 Hz, 1H), 3.83 (d, J=10.9 Hz, 1H), 2.97 (dd, J=17.7, 6.2 Hz, 1H), 2.50 (d, J=18.2 Hz, 1H); (APCI(+)) m/e 357 (M+H)+.


Example 268
5-[(4S)-4-hydroxy-2-oxopyrrolidin-1-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 250, substituting (S)-5-hydroxyoxazolidin-2-one for (R)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, methanol-d4) δ ppm 9.10 (t, J=5.7 Hz, 1H), 8.74 (d, J=7.0 Hz, 1H), 8.17 (d, J=2.0 Hz, 1H), 7.98 (d, J=2.1 Hz, 1H), 7.78 (s, 1H), 7.61 (d, J=4.2 Hz, 1H), 7.46 (d, J=7.0 Hz, 1H), 6.68 (d, J=4.2 Hz, 1H), 4.71 (s, 2H), 4.62 (t, J=5.7 Hz, 1H), 4.15 (dd, J=10.9, 5.3 Hz, 1H), 3.83 (d, J=11.0 Hz, 1H), 2.97 (dd, J=17.6, 6.2 Hz, 1H), 2.50 (d, J=16.8 Hz, 1H); (APCI(+)) m/e 357 (M+H)+.


Example 271
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(methylsulfonyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting methanesulfonyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, methanol-d4) δ ppm 8.39 (d, J=7.0 Hz, 1H), 7.79 (s, 1H), 7.60 (d, J=3.8 Hz, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.44 (s, 1H), 6.96 (d, J=3.8 Hz, 1H), 6.92 (dd, J=7.1, 1.2 Hz, 1H), 4.58 (bs, 2H), 3.85-3.76 (m, 2H), 3.03 (tt, J=11.8, 3.8 Hz, 1H), 2.97-2.82 (m, 5H), 2.18-2.09 (m, 2H), 1.96 (s, 1H), 1.86-1.71 (m, 2H); MS (ESI(+)) m/e 419 (M+H)+.


Example 274
N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide
Example 274A
tert-butyl 4-(3-(imidazo[1,2-a]pyridin-6-ylmethyl)ureido)phenylcarbamate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-aminophenylcarbamate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-6-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 274B
1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-6-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(3-(imidazo[1,2-a]pyridin-6-ylmethyl)ureido)phenylcarbamate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 274C
N-(4-{[(imidazo[1,2-a]pyridin-6-ylmethyl)carbamoyl]amino}phenyl)-4-methylpentanamide

The title compound was prepared as described in Example 1A, substituting 1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-6-ylmethyl)urea for 3-methylbutan-1-amine and 4-methylpentanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.70 (s, 1H), 8.50 (s, 1H), 8.43 (s, 1H), 7.94 (s, 1H), 7.53 (m, 2H), 7.43 (m, 2H), 7.30 (m, 2H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 6.61 (t, J=5.9 Hz, 1H), 4.28 (d, J=5.8 Hz, 2H), 2.26 (t, J=7.6 Hz, 2H), 1.60-1.40 (m, 3H), 0.89 (d, J=6.4 Hz, 6H); MS (ESI(+)) m/e 380 (M+H)+.


Table 15.


The following Examples were prepared essentially as described in Example 274, substituting the appropriate carboxylic acid in Example 274C.















Ex
Name

1H NMR

MS







275
3-cyclopentyl-N-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.69 (s,

(ESI(+))



(4-{[(imidazo[1,2-
1H), 8.48 (s, 1H), 8.43 (s, 1H), 7.94 (s, 1H),
m/e



a]pyridin-6-
7.53 (m, 2H), 7.43 (m, 2H), 7.30 (m, 2H),
406 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)propanamide
7.20 (dd, J = 9.2, 1.7 Hz, 1H), 6.60 (t, J = 5.9 Hz,




1H), 4.28 (d, J = 5.8 Hz, 2H), 2.26 (t, J = 7.6 Hz,




2H), 1.75 (m, 3H), 1.66-1.39 (m, 6H),




1.08 (m, 2H)


276
N-(4-

1H NMR (500 MHz, DMSO-d6) δ ppm 9.36 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.53 (s, 1H), 8.43 (s, 1H), 7.94 (s, 1H),
m/e



a]pyridin-6-
7.53 (m, 2H), 7.49 (m, 2H), 7.33 (m, 2H),
382 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
7.21 (dd, J = 9.2, 1.7 Hz, 1H), 6.62 (t, J = 5.9 Hz,



2-(propan-2-
1H), 4.28 (d, J = 5.9 Hz, 2H), 3.97 (s, 2H),



yloxy)acetamide
3.67 (m, 1H), 1.16 (d, J = 6.1 Hz, 6H)


277
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.50 (s, 1H), 8.44 (d, J = 1.5 Hz, 1H),
m/e



a]pyridin-6-
7.96 (s, 1H), 7.54 (m, 2H), 7.44 (m, 2H), 7.31 (m,
394 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
2H), 7.22 (dd, J = 9.2, 1.7 Hz, 1H), 6.61 (t, J = 5.9 Hz,



2-
1H), 4.28 (d, J = 5.9 Hz, 2H), 4.12 (m,



(tetrahydrofuran-
1H), 3.74 (m, 1H), 3.60 (m, 1H), 2.47 (m, 1H),



2-yl)acetamide
2.39 (m, 1H), 1.98 (m, 1H), 1.81 (m, 2H),




1.49 (m, 1H)


278
N-(4-

1H NMR (500 MHz, DMSO-d6) δ ppm 9.72 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.50 (s, 1H), 8.43 (s, 1H), 7.94 (s, 1H),
m/e



a]pyridin-6-
7.53 (m, 2H), 7.43 (m, 2H), 7.31 (m, 2H),
408 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
7.21 (dd, J = 9.2, 1.7 Hz, 1H), 6.60 (t, J = 5.9 Hz,



2-(tetrahydro-
1H), 4.28 (d, J = 5.9 Hz, 2H), 3.82 (m, 2H),



2H-pyran-4-
3.29 (m, 2H), 2.20 (d, J = 7.1 Hz, 2H), 2.01 (m,



yl)acetamide
1H), 1.57 (m, 2H), 1.25 (m, 2H)


279
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.49 (s, 1H), 8.42 (s, 1H), 7.94 (s, 1H),
m/e



a]pyridin-6-
7.53 (m, 2H), 7.42 (m, 2H), 7.35-7.15 (m, 8H),
414 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
6.60 (t, J = 5.9 Hz, 1H), 4.28 (d, J = 5.8 Hz,



3-
2H), 2.89 (t, J = 7.3 Hz, 2H), 2.57 (t, J = 5.7 Hz,



phenylpropanamide
2H)


280
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.69 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.52 (s, 1H), 8.47 (d, J = 7.0 Hz, 1H),
m/e



a]pyridin-7-
7.87 (s, 1H), 7.50 (bs, 1H), 7.42 (m, 2H), 7.37 (s,
380 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
1H), 7.30 (m, 2H), 6.82 (dd, J = 7.0, 1.5 Hz,



4-
1H), 6.63 (t, J = 6.0 Hz, 1H), 4.31 (d, J = 5.9 Hz,



methylpentanamide
2H), 2.25 (t, J = 7.6 Hz, 2H),




1.60-1.41 (m, 3H), 0.88 (d, J = 6.4 Hz, 6H)


281
3-cyclopentyl-N-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.69 (s,

(ESI(+))



(4-{[(imidazo[1,2-
1H), 8.53 (s, 1H), 8.48 (d, J = 6.9 Hz, 1H),
m/e



a]pyridin-7-
7.88 (bs, 1H), 7.52 (bs, 1H), 7.44 (m, 2H), 7.37 (s,
406 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)propanamide
1H), 7.31 (m, 2H), 6.83 (dd, J = 6.9, 1.4 Hz,




1H), 6.64 (t, J = 6.0 Hz, 1H), 4.32 (d, J = 5.9 Hz,




2H), 2.27 (t, J = 7.6 Hz, 2H), 1.74 (m, 3H),




1.65-1.40 (m, 6H), 1.09 (m, 2H)


282
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.37 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.59 (s, 1H), 8.49 (m, 1H), 7.89 (s, 1H),
m/e



a]pyridin-7-
7.50 (m, 3H), 7.39 (s, 1H), 7.34 (m, 2H),
382 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
6.84 (dd, J = 6.9, 1.6 Hz, 1H), 6.68 (t, J = 6.0 Hz,



2-(propan-2-
1H), 4.33 (d, J = 6.0 Hz, 2H), 3.98 (s, 2H),



yloxy)acetamide
3.67 (m, 1H), 1.16 (d, J = 6.1 Hz, 6H)


283
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.54 (s, 1H), 8.48 (d, J = 7.0 Hz, 1H),
m/e



a]pyridin-7-
7.88 (s, 1H), 7.51 (s, 1H), 7.44 (m, 2H), 7.38 (bs,
394 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
1H), 7.32 (m, 2H), 6.83 (dd, J = 6.9, 1.6 Hz,



2-
1H), 6.65 (t, J = 6.0 Hz, 1H), 4.32 (d, J = 5.9 Hz,



(tetrahydrofuran-
2H), 4.16 (m, 1H), 3.76 (m, 1H), 3.60 (m,



2-yl)acetamide
1H), 2.50 (m, 1H), 2.39 (m, 1H), 1.99 (m, 1H),




1.83 (m, 2H), 1.53 (m, 1H)


284
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.72 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.53 (s, 1H), 8.48 (d, J = 6.9 Hz, 1H),
m/e



a]pyridin-7-
7.88 (bs, 1H), 7.51 (bs, 1H), 7.44 (m, 2H), 7.38 (bs,
408 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
1H), 7.32 (m, 2H), 6.83 (m, 1H), 6.65 (m, 1H),



2-(tetrahydro-
4.32 (m, 2H), 3.82 (m, 2H), 3.33 (m, 2H),



2H-pyran-4-
2.20 (d, J = 7.1 Hz, 2H), 1.97 (m, 1H), 1.58 (m, 2H),



yl)acetamide
1.23 (m, 2H)


285
N-(4-

1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (s,

(ESI(+))



{[(imidazo[1,2-
1H), 8.54 (s, 1H), 8.49 (d, J = 6.9 Hz, 1H),
m/e



a]pyridin-7-
7.89 (bs, 1H), 7.52 (bs, 1H), 7.42 (m, 3H),
414 (M + H)+



ylmethyl)carbamoyl]amino}phenyl)-
7.35-7.22 (m, 6H), 7.17 (m, 1H), 6.84 (d, J = 7.6 Hz,



3-
1H), 6.65 (t, J = 6.0 Hz, 1H), 4.32 (d, J = 5.9 Hz,



phenylpropanamide
2H), 2.90 (t, J = 7.7 Hz, 2H), 2.58 (t, J = 7.7 Hz,




2H)









Example 290
tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate
Example 290A
1-(4-bromo-2-fluorophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1C, substituting 4-bromo-2-fluoroaniline for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 290B
tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromo-2-fluorophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.53-8.46 (m, 2H), 8.09 (t, J=8.7 Hz, 1H), 7.91-7.88 (m, 1H), 7.54-7.50 (m, 1H), 7.42-7.37 (m, 1H), 7.33-7.24 (m, 1H), 7.21-7.08 (m, 2H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 6.17-6.10 (m, 1H), 4.35 (d, J=5.8 Hz, 2H), 4.01-3.94 (m, 2H), 3.55-3.47 (m, 2H), 2.46-2.36 (m, 2H), 1.42 (s, 9H); MS (ESI(+)) m/e 466 (M+H)+.


Example 291
tert-butyl (3S)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate
Example 291A
(5)-tert-butyl 3-(4-nitrophenoxy)pyrrolidine-1-carboxylate

(5)-Tert-butyl 3-hydroxypyrrolidine-1-carboxylate (10 g, 53.4 mmol) was dissolved in 1-fluoro-4-nitrobenzene (13.94 g, 99 mmol). An aqueous solution of 5.9N potassium hydroxide (77 ml, 452 mmol) was added followed by addition of tetrabutylammonium bromide (2.238 g, 6.94 mmol). The reaction mixture was stirred at 40° C. for 24 hours and then cooled, diluted with water and extracted with ethyl acetate. The combined organic layers were dried with sodium sulfate, filtered and concentrated to give the title compound.


Example 291B
(5)-tert-butyl 3-(4-aminophenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting (5)-tert-butyl 3-(4-nitrophenoxy)pyrrolidine-1-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 291C
tert-butyl (3S)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting (5)-tert-butyl 3-(4-aminophenoxy)pyrrolidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (300 MHz, DMSO-d6) δ ppm 8.51-8.44 (m, 2H), 7.88-7.86 (m, 1H), 7.53-7.49 (m, 1H), 7.40-7.27 (m, 3H), 6.86-6.80 (m, 3H), 6.63 (t, J=6.0 Hz, 1H), 4.93-4.84 (m, 1H), 4.32 (d, J=6.0 Hz, 2H), 3.55-3.28 (m, 4H), 2.16-1.94 (m, 2H), 1.42-1.36 (m, 9H); MS (ESI(+)) m/e 452 (M+H)+.


Example 292
tert-butyl {2-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}carbamate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(tert-butoxycarbonylamino)-3-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.26 (s, 1H), 9.08 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.91-7.78 (m, 2H), 7.76-7.68 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (bs, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.49 (d, J=5.8 Hz, 2H), 1.48 (s, 9H); MS (ESI(+)) m/e 385 (M+H)+.


Example 297
2-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide
Example 297A
tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 4-bromoaniline.


Example 297B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1,2,3,6-tetrahydropyridin-4-yl)thiazole-5-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 297C
2-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1,2,3,6-tetrahydropyridin-4-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.27 (t, J=5.9 Hz, 1H), 8.50 (d, J=7.1 Hz, 1H), 8.41 (s, 1H), 7.89 (s, 1H), 7.38-7.56 (m, 7H), 6.85 (dd, J=6.8, 1.7 Hz, 1H), 6.56-6.89 (m, 1H), 4.49 (d, J=5.8 Hz, 2H), 4.08-4.40 (m, 2H), 3.74-3.92 (m, 1H), 3.44-3.66 (m, 1H), 2.66 (s, 2H); MS (ESI(+)) m/e 444 (M+H)+.


Example 298
4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
Example 298A
4-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-bromobenzoic acid for 4-nitrobenzoic acid.


Example 298B
4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 51A, substituting 1-(2-hydroxy-2-methylpropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.05 (t, J=5.9 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.19 (d, J=0.8 Hz, 1H), 7.97 (d, J=0.7 Hz, 1H), 7.95-7.86 (m, 3H), 7.73-7.66 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.42-7.37 (m, 1H), 6.87 (dd, J=7.0, 1.7 Hz, 1H), 4.73 (s, 1H), 4.51 (d, J=5.8 Hz, 2H), 4.04 (s, 2H), 1.10 (s, 6H); MS (ESI(+)) m/e 390 (M+H)+.


Example 299
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-phenylthiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.14 (t, J=6.0 Hz, 1H), 8.50 (dd, J=7.1, 0.7 Hz, 1H), 7.91-7.88 (m, 1H), 7.84 (d, J=3.9 Hz, 1H), 7.72 (dt, J=8.3, 2.4 Hz, 2H), 7.57 (d, J=3.9 Hz, 1H), 7.53 (d, J=1.2 Hz, 1H), 7.49-7.33 (m, 4H), 6.86 (dd, J=7.0, 1.7 Hz, 1H), 4.50 (d, J=5.8 Hz, 2H); MS (ESI(+)) m/e 334 (M+H).


Example 301
tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.06 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.87 (m, 3H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (m, 3H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.50 (d, J=5.9 Hz, 2H), 3.72 (dd, J=10.3, 7.5 Hz, 1H), 3.47 (m, 2H), 3.20 (m, 2H), 2.21 (m, 1H), 1.97 (m, 1H), 1.41 (m, 9H); (ESI(+)) m/e 421 (M+H)+.


Example 302
tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 3-(4-aminophenyl)pyrrolidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (400 MHz, DMSO-d6) δ ppm 8.61 (s, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (d, J=1.1 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.36 (m, 3H), 7.14 (m, 2H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 6.69 (t, J=6.0 Hz, 1H), 4.33 (d, J=6.0 Hz, 2H), 3.65 (dd, J=10.2, 7.5 Hz, 1H), 3.46 (m, 1H), 3.21 (m, 2H), 3.09 (m, 1H), 2.12 (m, 1H), 1.89 (m, 1H), 1.41 (m, 9H); (ESI(+)) m/e 436 (M+H)+.


Example 303
N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)biphenyl-2-sulfonamide
Example 303A
tert-butyl 4-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)phenylcarbamate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-aminophenylcarbamate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 303B
1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)phenylcarbamate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 303C
N-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)biphenyl-2-sulfonamide

In a 4 mL vial was mixed 1-(4-aminophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea (50 mg, 0.178 mmol) in anhydrous tetrahydrofuran (2 mL). To this mixture at room temperature was added 60% sodium hydride (24.88 mg, 0.622 mmol). The reaction was stirred about 30 minutes and biphenyl-2-sulfonyl chloride (53.9 mg, 0.213 mmol) was added. The reaction mixture stirred overnight at room temperature and was quenched with saturated ammonium chloride and water. The aqueous solution was extracted with dichloromethane and 10% methanol/dichloromethane. The organic layers were combined, concentrated and purified by normal phase chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (bs, 1H), 8.56 (s, 1H), 8.47 (dd, J=6.9, 0.9 Hz, 1H), 7.95 (dd, J=7.8, 1.4 Hz, 1H), 7.87 (dd, J=1.2, 0.6 Hz, 1H), 7.62 (m, 1H), 7.54 (m, 1H), 7.51 (m, 1H), 7.38 (m, 4H), 7.30-7.20 (m, 5H), 6.82 (m, 3H), 6.66 (t, J=6.0 Hz, 1H), 4.30 (d, J=6.0 Hz, 2H); (ESI(+)) m/e 498 (M+H)+.


Example 306
1-{2-fluoro-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
Example 306A
1-(2-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 306B
1-{2-fluoro-4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(2-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, methanol-d4) δ ppm 8.74 (d, J=7.0 Hz, 1H), 8.19-8.15 (m, 1H), 8.00-7.96 (m, 1H), 7.92 (t, J=8.5 Hz, 1H), 7.81-7.77 (m, 1H), 7.50-7.44 (m, 1H), 7.28-7.16 (m, 2H), 6.17-6.11 (m, 1H), 4.61 (bs, 2H), 4.30-4.15 (m, 2H), 3.79 (t, J=5.7 Hz, 2H), 3.08-2.90 (m, 1H), 2.62-2.45 (m, 2H), 1.17-1.08 (m, 6H); MS (ESI(+)) m/e 436 (M+H)+.


Example 307
1-{2-fluoro-4-[1-(tetrahydrofuran-2-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(2-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and tetrahydrofuran-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, methanol-d4) δ ppm 8.74 (d, J=7.0 Hz, 1H), 8.17 (d, J=2.2 Hz, 1H), 7.98 (d, J=2.2 Hz, 1H), 7.92 (t, J=8.5 Hz, 1H), 7.80 (bs, 1H), 7.47 (dd, J=7.0, 1.5 Hz, 1H), 7.28-7.16 (m, 2H), 6.17-6.09 (m, 1H), 4.84-4.70 (m, 1H), 4.61 (bs, 2H), 4.34-4.12 (m, 2H), 4.01-3.68 (m, 4H), 2.67-2.47 (m, 2H), 2.29-1.88 (m, 4H); MS (ESI(+)) m/e 464 (M+H)+.


Example 314
tert-butyl 4-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxo ethyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate
Example 314A
2-(4-bromophenyl)-N-(imidazo[1,2-a]pyridin-6-yl)acetamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-amine for 3-methylbutan-1-amine and 2-(4-bromophenyl)acetic acid for 4-nitrobenzoic acid.


Example 314B
tert-butyl 4-{4-[2-(imidazo[1,2-a]pyridin-6-ylamino)-2-oxo ethyl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 2-(4-bromophenyl)-N-(imidazo[1,2-a]pyridin-6-yl)acetamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.25 (s, 1H), 9.20-9.16 (m, 1H), 7.98-7.94 (m, 1H), 7.58-7.48 (m, 2H), 7.44-7.36 (m, 2H), 7.35-7.28 (m, 2H), 7.16 (dd, J=9.6, 2.0 Hz, 1H), 6.16-6.09 (m, 1H), 4.05-3.94 (m, 2H), 3.66 (s, 2H), 3.53 (t, J=5.7 Hz, 2H), 2.49-2.40 (m, 2H), 1.42 (s, 9H); MS (ESI(+)) m/e 433 (M+H)+.


Example 315
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]benzamide

The title compound was prepared as described in Example 51A, substituting 4-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04 (t, J=5.9 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 8.27 (s, 1H), 8.00-7.86 (m, 4H), 7.69 (d, J=8.4 Hz, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (d, J=1.5 Hz, 1H), 6.87 (dd, J=7.0, 1.7 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 3.94 (d, J=7.1 Hz, 2H), 2.15 (dp, J=13.6, 6.8 Hz, 1H), 0.87 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 374 (M+H)+.


Example 318
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(propan-2-yloxy)phenyl]thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 2-(3-isopropoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04 (t, J=6.0 Hz, 1H), 8.49 (dd, J=7.0, 0.8 Hz, 1H), 8.19 (d, J=0.4 Hz, 1H), 7.89 (d, J=0.8 Hz, 1H), 7.86 (d, J=0.5 Hz, 1H), 7.75 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.24 (d, J=3.9 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.48 (d, J=5.8 Hz, 2H), 4.13 (d, J=6.6 Hz, 2H), 3.09-2.83 (m, 4H), 2.47-2.40 (m, 1H), 2.14-1.96 (m, 1H), 1.88-1.69 (m, 1H), 1.69-1.54 (m, 1H), 1.37-1.14 (m, 1H).


Example 319
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1,2,3,6-tetrahydropyridin-4-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and tetrahydro-2H-pyran-4-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.26 (t, J=5.9 Hz, 1H), 8.50 (d, J=6.8 Hz, 1H), 8.40 (s, 1H), 7.89 (s, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.42 (s, 1H), 6.84 (dd, J=7.1, 1.7 Hz, 1H), 6.72-6.79 (m, 1H), 4.49 (d, J=5.8 Hz, 2H), 4.32 (s, 1H), 4.16 (s, 1H), 3.81-3.89 (m, 2H), 3.73 (s, 2H), 3.36-3.47 (m, 1H), 2.83-3.05 (m, 1H), 2.65 (s, 1H), 2.38-2.54 (m, 2H), 1.50-1.69 (m, 4H); MS (ESI(+)) m/e 452 (M+H)+.


Example 320
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1,2,3,6-tetrahydropyridin-4-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.26 (t, J=5.9 Hz, 1H), 8.50 (d, J=7.1 Hz, 1H), 8.40 (s, 1H), 7.89 (s, 1H), 7.53 (s, 1H), 7.42 (s, 1H), 6.84 (dd, J=7.1, 1.7 Hz, 1H), 6.76 (s, 1H), 4.49 (d, J=5.8 Hz, 2H), 4.29 (s, 1H), 4.16 (s, 1H), 3.62-3.74 (m, 2H), 2.81-3.03 (m, 1H), 2.60-2.69 (m, 1H), 2.50-2.58 (m, 1H), 1.02 (d, J=6.4 Hz, 6H); MS (ESI(+)) m/e 410 (M+H)+.


Example 321
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide
Example 321A
(5)-tert-butyl 3-(4-(benzyloxycarbonyl)phenoxy)pyrrolidine-1-carboxylate

To a stirred solution of (R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1 g, 5.34 mmol) in tetrahydrofuran (38.1 ml) was added benzyl 4-hydroxybenzoate (1.341 g, 5.87 mmol) and triphenylphpsphine polymer bound (4.45 g, 8.01 mmol). The reaction mixture was cooled to 0° C. and a solution of (E)-diisopropyl diazene-1,2-dicarboxylate (1.367 ml, 6.94 mmol) in tetrahydrofuran (5 mL) was added dropwise over 15 minutes. The reaction was allowed to stir at room temperature for 16 hours and the mixture was filtered. The solids were washed with dichloromethane, and the combined filtrates were concentrated and purified by normal phase chromatography to give the title compound.


Example 321B
(S)-4-(1-(tert-butoxycarbonyl)pyrrolidin-3-yloxy)benzoic acid

The title compound was prepared as described in Example 1B, substituting (R)-tert-butyl 3-(4-(benzyloxycarbonyl)phenoxy)pyrrolidine-1-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 321C
(5)-tert-butyl 3-(4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)phenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and (S)-4-(1-(tert-butoxycarbonyl)pyrrolidin-3-yloxy)benzoic acid for 4-nitrobenzoic acid.


Example 321D
(S)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide

The title compound was prepared as described in Example 28A, substituting (S)-tert-butyl 3-(4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)phenoxy)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 321E
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide

The title compound was prepared as described in Example 1A, substituting (S)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide for 3-methylbutan-1-amine and (S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6, Temp=90° C.) δ ppm 8.67-8.59 (m, 1H), 8.41 (d, J=6.9 Hz, 1H), 7.90-7.84 (m, 2H), 7.81 (s, 1H), 7.50-7.46 (m, 1H), 7.38 (s, 1H), 7.03-6.97 (m, 2H), 6.83 (dd, J=6.9, 1.7 Hz, 1H), 5.17-5.04 (m, 1H), 4.49 (d, J=5.9 Hz, 2H), 3.91-3.36 (m, 5H), 2.31-1.98 (m, 2H), 1.63-1.49 (m, 1H), 1.38-1.23 (m, 1H), 1.00 (d, J=6.7 Hz, 3H), 0.89-0.74 (m, 3H); MS (ESI(+)) m/e 421 (M+H)+.


Table 16.


The following Examples were prepared essentially as described in Example 321, substituting the appropriate carboxylic acid in Example 321E.














Ex
Name
MS







339
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3R)-
(ESI(+))



tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide
m/e




435 (M + H)+


340
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2R)-
(ESI(+))



tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide
m/e




435 (M + H)+


341
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(2S)-
(ESI(+))



tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide
m/e




435 (M + H)+


342
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-
(ESI(+))



pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}benzamide
m/e




449 (M + H)+


343
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(tetrahydro-2H-
(ESI(+))



pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}benzamide
m/e




463 (M + H)+


346
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3S)-1-[(3S)-
(ESI(+))



tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide
m/e




435 (M + H)+


347
4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




419 (M + H)+


348
4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}-
(ESI(+))



N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




423 (M + H)+


349
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(3-methoxy-2-
(ESI(+))



methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide
m/e




437 (M + H)+


350
4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)benzamide
m/e




407 (M + H)+


351
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3S)-1-(2-
(ESI(+))



methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide
m/e




407 (M + H)+


352
4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




405 (M + H)+


353
4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e




441 (M + H)+


354
4-{[(3S)-1-(3-hydroxy-3-methylbutanoyl)pyrrolidin-3-yl]oxy}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e




437 (M + H)+









Example 322
tert-butyl 4-[4-(imidazo[1,2-a]pyridin-7-ylcarbamoyl)phenyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-amine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.36 (s, 1H), 8.47 (d, J=7.3 Hz, 1H), 8.15-8.10 (m, 1H), 7.94-7.87 (m, 2H), 7.83 (s, 1H), 7.50-7.40 (m, 3H), 7.24 (dd, J=7.3, 2.1 Hz, 1H), 4.16-4.05 (m, 2H), 2.94-2.66 (m, 3H), 1.84-1.73 (m, 2H), 1.65-1.41 (m, 11H); MS (ESI(+)) m/e 421 (M+H)+.


Example 323
tert-butyl 4-[4-(imidazo[1,2-a]pyridin-6-ylcarbamoyl)phenyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-amine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.27 (s, 1H), 9.36-9.31 (m, 1H), 8.03 (s, 1H), 7.95-7.88 (m, 2H), 7.60-7.52 (m, 2H), 7.47-7.35 (m, 3H), 4.15-4.04 (m, 2H), 2.95-2.66 (m, 3H), 1.83-1.73 (m, 2H), 1.65-1.45 (m, 2H), 1.42 (s, 9H); MS (ESI(+)) m/e 421 (M+H)+.


Example 324
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(2-methylpropanoyl)amino]oxetan-3-yl}thiophene-2-carboxamide
Example 324A
5-(3-(1,1-dimethylethylsulfinamido)oxetan-3-yl)thiophene-2-carboxylic acid

Butyllithium (6.16 ml, 15.41 mmol) was added dropwise to a stirred solution of diisopropylamine (1.919 ml, 13.69 mmol) in tetrahydrofuran (10 ml) at −78° C. The solution was allowed to warm to room temperature and then added dropwise by syringe to a stirred −78° C. solution of thiophene-2-carboxylic acid (0.877 g, 6.85 mmol) in tetrahydrofuran (30 ml). The resulting suspension was stirred for 40 minutes at −78° C. when a solution of 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (1 g, 5.71 mmol) in tetrahydrofuran (10 ml) was added dropwise. After the addition was complete, the reaction mixture was allowed to warm to room temperature, quenched with saturated ammonium chloride and diluted with a water to dissolve the remaining solids. The aqueous solution was extracted with ethyl acetate, adjusted to pH 2 by addition of 1N aqueous hydrochloric acid and re-extracted with ethyl acetate and methylene chloride. The organic extracts were dried with magnesium sulfate, filtered, concentrated and purified by normal phase chromatography to give the title compound.


Example 324B
5-(3-(1,1-dimethylethylsulfinamido)oxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(3-(1,1-dimethylethylsulfinamido)oxetan-3-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 324C
5-(3-aminooxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

5-(3-(1,1-Dimethylethylsulfinamido)oxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide (432 mg, 1 mmol) in 10 ml methanol was treated with 4N aqueous HCl in dioxane (0.75 ml, 3 mmol) and the mixture was stirred for 2 hours. Concentration provided the title compound.


Example 324D

The title compound was prepared as described in Example 1A, substituting 5-(3-aminooxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03-9.10 (m, 2H), 8.48 (d, J=7.1 Hz, 1H), 7.89 (s, 1H), 7.71 (d, J=4.0 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.38 (s, 1H), 7.22 (d, J=4.0 Hz, 1H), 6.83 (dd, J=6.9, 1.8 Hz, 1H), 4.80 (d, J=6.7 Hz, 2H), 4.71 (d, J=6.7 Hz, 2H), 4.46 (d, J=6.0 Hz, 2H), 2.40-2.48 (m, 1H), 1.05 (d, J=7.1 Hz, 6H); MS (ESI(+)) m/e 399 (M+H)+.


Example 325
5-[3-(benzoylamino)oxetan-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-aminooxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.70 (s, 1H), 9.05 (t, J=5.9 Hz, 1H), 8.47 (d, J=6.8 Hz, 1H), 7.87-7.93 (m, 3H), 7.72 (d, J=3.7 Hz, 1H), 7.56-7.62 (m, 1H), 7.48-7.55 (m, 3H), 7.37 (s, 1H), 7.29 (d, J=3.7 Hz, 1H), 6.82 (dd, J=7.1, 1.7 Hz, 1H), 5.01 (d, J=6.8 Hz, 2H), 4.80 (d, J=7.1 Hz, 2H), 4.45 (d, J=5.8 Hz, 2H); MS (ESI(+)) m/e 433 (M+H)+.


Example 326
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{3-[(tetrahydrofuran-3-ylacetyl)amino]oxetan-3-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-aminooxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 2-(tetrahydrofuran-3-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.22 (s, 1H), 9.07 (t, J=6.0 Hz, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.89 (s, 1H), 7.71 (d, J=3.6 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.38 (s, 1H), 7.22 (d, J=4.0 Hz, 1H), 6.83 (dd, J=7.1, 1.6 Hz, 1H), 4.81 (d, J=6.7 Hz, 2H), 4.72 (d, J=6.7 Hz, 2H), 4.46 (d, J=6.0 Hz, 2H), 3.56-3.80 (m, 3H), 2.23-2.30 (m, 2H), 1.89-2.04 (m, 1H), 1.45-1.58 (m, 1H); MS (ESI(+)) m/e 441 (M+H)+.


Example 327
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[3-(pentanoylamino)oxetan-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-aminooxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and pentanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.11 (s, 1H), 9.05 (t, J=5.9 Hz, 1H), 8.48 (dd, J=7.0, 0.8 Hz, 1H), 7.88 (s, 1H), 7.70 (d, J=4.1 Hz, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.38 (s, 1H), 7.21 (d, J=3.7 Hz, 1H), 6.83 (dd, J=7.1, 1.7 Hz, 1H), 4.80 (d, J=6.8 Hz, 2H), 4.71 (d, J=6.8 Hz, 2H), 4.46 (d, J=5.8 Hz, 2H), 2.17 (t, J=7.5 Hz, 2H), 1.44-1.57 (m, 2H), 1.22-1.37 (m, 2H), 0.84-0.92 (m, 3H); MS (ESI(+)) m/e 413 (M+H)+.


Example 328
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl]oxy)phenyl}urea
Example 328A
(R)-tert-butyl 3-(4-nitrophenoxy)pyrrolidine-1-carboxylate

(R)-Tert-butyl 3-hydroxypyrrolidine-1-carboxylate (10 g, 53.4 mmol) was dissolved in 1-fluoro-4-nitrobenzene (13.94 g, 99 mmol). An aqueous solution of 5.9N potassium hydroxide (77 ml, 452 mmol) was added followed by addition of tetrabutylammonium bromide (2.238 g, 6.94 mmol). The reaction mixture was stirred at 40° C. for 24 hours, cooled, diluted with water and extracted with ethyl acetate. The combined organic layers were dried with sodium sulfate, filtered and concentrated to give the title compound.


Example 328B
(R)-tert-butyl 3-(4-aminophenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting (R)-tert-butyl 3-(4-nitrophenoxy)pyrrolidine-1-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 328C
tert-butyl (3S)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting (R)-tert-butyl 3-(4-aminophenoxy)pyrrolidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 328D
(R)-1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(pyrrolidin-3-yloxy)phenyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl (3S)-3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 328E
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]urea

The title compound was prepared as described in Example 1A, substituting (R)-1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(pyrrolidin-3-yloxy)phenyl)urea for 3-methylbutan-1-amine and (S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.76-8.70 (m, 1H), 8.19-8.12 (m, 1H), 8.00-7.94 (m, 1H), 7.81-7.75 (m, 1H), 7.46 (d, J=7.0 Hz, 1H), 7.34-7.25 (m, 2H), 6.92-6.82 (m, 2H), 5.07-4.95 (m, 1H), 4.58 (bs, 2H), 3.84-3.61 (m, 3H), 3.60-3.45 (m, 1H), 2.67-2.45 (m, 1H), 2.31-2.06 (m, 2H), 1.72-1.57 (m, 1H), 1.50-1.35 (m, 1H), 1.12-1.00 (m, 3H), 0.94-0.85 (m, 3H); MS (ESI(+)) m/e 436 (M+H)+.


Table 17.


The following Examples were prepared essentially as described in Example 328, substituting the appropriate alcohol in Example 328A and the appropriate carboxylic acid in Example 328E.














Ex
Name
MS







329
1-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)urea
m/e




456 (M + H)+


330
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(2-
(ESI(+))



methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)urea
m/e




422 (M + H)+


331
1-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




420 (M + H)+


332
1-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




434 (M + H)+


333
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-
(ESI(+))



pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea
m/e




464 (M + H)+


334
1-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-
(ESI(+))



yl]oxy}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




438 (M + H)+


335
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2R)-
(ESI(+))



tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea
m/e




450 (M + H)+


336
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[(2S)-
(ESI(+))



tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]urea
m/e




450 (M + H)+


337
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-
(ESI(+))



(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)urea
m/e




450 (M + H)+


338
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[(3R)-1-(tetrahydro-2H-
(ESI(+))



pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)urea
m/e




478 (M + H)+


689
1-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




474 (M + H)+


690
1-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




474 (M + H)+


691
1-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




474 (M + H)+


692
1-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




492 (M + H)+


693
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-({(3R)-1-[4-
(ESI(+))



(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]urea
m/e




524 (M + H)+


694
1-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




492 (M + H)+


695
1-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




490 (M + H)+


696
1-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-3-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e




490 (M + H)+









Example 355
2-(4-benzoylpiperazin-1-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 53B, substituting phenyl(piperazin-1-yl)methanone for 4-cyanobenzylamine and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.86 (t, J=6.0 Hz, 1H), 8.48 (d, J=6.7 Hz, 1H), 7.90 (s, 1H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.41-7.50 (m, 5H), 7.37 (s, 1H), 6.82 (dd, J=7.1, 1.6 Hz, 1H), 4.43 (d, J=5.6 Hz, 2H), 3.41-3.82 (m, 8H); MS (ESI(+)) m/e 447 (M+H)+.


Example 356
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(propan-2-yl)piperazin-1-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 53B, substituting 1-isopropylpiperazine for 4-cyanobenzylamine and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.80 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.87 (s, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.37 (s, 1H), 6.81 (dd, J=7.1, 1.7 Hz, 1H), 4.42 (d, J=6.1 Hz, 2H), 3.41-3.48 (m, 4H), 2.64-2.79 (m, 1H), 2.51-2.57 (m, 4H), 0.98 (d, J=6.4 Hz, 6H); MS (ESI(+)) m/e 385 (M+H)+.


Example 357
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[4-(2-methoxyethyl)piperazin-1-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as in Example 53B, substituting 1-(2-methoxyethyl)piperazine for 4-cyanobenzylamine and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 2-bromo-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.82 (t, J=6.0 Hz, 1H), 8.48 (d, J=6.7 Hz, 1H), 7.88 (s, 1H), 7.88 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 6.81 (dd, J=7.1, 1.6 Hz, 1H), 4.43 (d, J=6.0 Hz, 2H), 3.42-3.48 (m, 6H), 3.24 (s, 3H), 2.51-2.56 (m, 6H); MS (ESI(+)) m/e 401 (M+H)+.


Example 358
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide
Example 358A
methyl 4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)benzoate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(methoxycarbonyl)benzoic acid for 4-nitrobenzoic acid.


Example 358B
4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)benzoic acid

The title compound was prepared as described in Example 4B, substituting methyl 4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)benzoate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 358C
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide

The title compound was prepared as described in Example 1A, substituting 3-methylbutan-1-amine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.15 (t, J=5.8 Hz, 1H), 8.55-8.47 (m, 2H), 8.00-7.84 (m, 5H), 7.54 (dd, J=5.1, 4.1 Hz, 2H), 7.23 (dd, J=9.3, 1.7 Hz, 1H), 4.48 (d, J=5.8 Hz, 2H), 3.30-3.21 (m, 2H), 1.62 (dp, J=13.3, 6.6 Hz, 1H), 1.49-1.37 (m, 2H), 0.91 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 365 (M+H)+.


Example 359
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide

The title compound was prepared as described in Example 1A, substituting (5)-(tetrahydrofuran-3-yl)methanamine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-6-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.15 (t, J=5.8 Hz, 1H), 8.68 (t, J=5.7 Hz, 1H), 8.49 (bs, 1H), 8.03-7.85 (m, 5H), 7.58-7.50 (m, 2H), 7.23 (dd, J=9.1, 1.7 Hz, 1H), 4.49 (d, J=5.8 Hz, 2H), 3.80-3.56 (m, 4H), 3.48 (dd, J=8.5, 5.2 Hz, 1H), 3.28-3.17 (m, 1H), 2.03-1.87 (m, 1H), 1.68-1.46 (m, 1H), 1.37-1.09 (m, 1H); MS (ESI(+)) m/e 379 (M+H)+.


Example 360
1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea
Example 360A
1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-6-ylmethyl)urea

The title compound was prepared as described in Example 3A, substituting 1-isocyanato-4-bromobenzene for 1-isocyanato-4-nitrobenzene and imidazo[1,2-a]pyridin-6-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 360B
1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea

The title compound was prepared as described in Example 51A, substituting 1-propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-6-ylmethyl)urea for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.59 (s, 1H), 8.44 (s, 1H), 8.04 (s, 1H), 7.95 (s, 1H), 7.76 (s, 1H), 7.57-7.50 (m, 2H), 7.48-7.32 (m, 4H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 6.65 (t, J=5.9 Hz, 1H), 4.30 (d, J=5.8 Hz, 2H), 4.04 (t, J=6.9 Hz, 2H), 1.87-1.73 (m, 2H), 0.84 (t, J=7.3 Hz, 3H); MS (ESI(+)) m/e 375 (M+H)+.


Example 361
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-phenyl-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 51A, substituting phenyl boronic acid for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.34 (t, J=5.8 Hz, 1H), 8.56-8.48 (m, 2H), 8.05-7.95 (m, 2H), 7.90 (d, J=0.8 Hz, 1H), 7.60-7.49 (m, 4H), 7.45 (s, 1H), 6.87 (dd, J=7.0, 1.6 Hz, 1H), 4.52 (d, J=5.7 Hz, 2H); MS (ESI(+)) m/e 335 (M+H).


Example 362
1-(imidazo[1,2-a]pyridin-6-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea

The title compound was prepared as described in Example 51A, substituting 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-6-ylmethyl)urea for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.59 (s, 1H), 8.44 (d, J=1.6 Hz, 1H), 8.03 (d, J=0.8 Hz, 1H), 7.97-7.93 (m, 1H), 7.77 (d, J=0.8 Hz, 1H), 7.57-7.50 (m, 2H), 7.44-7.35 (m, 4H), 7.21 (dd, J=9.2, 1.7 Hz, 1H), 6.65 (t, J=5.9 Hz, 1H), 4.30 (d, J=5.8 Hz, 2H), 3.90 (d, J=7.2 Hz, 2H), 2.19-2.06 (m, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 389 (M+H)+.


Example 364
tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.48 (m, 1H), 7.88 (s, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.39 (m, 3H), 7.19 (m, 2H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.70 (t, J=6.0 Hz, 1H), 4.33 (d, J=6.0 Hz, 2H), 4.20 (m, 2H), 3.78 (m, 2H), 3.71 (m, 1H), 1.40 (s, 9H); (ESI(+)) m/e 422 (M+H)+.


Example 365
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.95 (t, J=6.0 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 7.06 (m, 2H), 6.85 (dd, J=7.0, 1.6 Hz, 1H), 4.67 (m, 1H), 4.49 (d, J=5.9 Hz, 2H), 3.67 (m, 2H), 3.18 (m, 2H), 1.92 (m, 2H), 1.52 (m, 2H), 1.41 (s, 9H); (ESI(+)) m/e 451 (M+H)+.


Example 366
tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47 (m, 2H), 7.88 (d, J=1.1 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 7.30 (m, 2H), 6.85 (m, 3H), 6.62 (t, J=6.0 Hz, 1H), 4.42 (m, 1H), 4.32 (d, J=6.0 Hz, 2H), 3.64 (m, 2H), 3.15 (m, 2H), 1.86 (m, 2H), 1.51 (m, 2H), 1.40 (s, 9H); (ESI(+)) m/e 466 (M+H)+.


Example 367
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]benzamide
Example 367A
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 367B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (m, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.42 (m, 3H), 6.85 (dd, J=7.0, 1.6 Hz, 1H), 4.50 (d, J=5.9 Hz, 2H), 3.90-3.66 (m, 1H), 3.63-3.20 (m, 4H), 2.70 (m, 1H), 2.38-2.18 (m, 1H), 2.10-1.90 (m, 1H), 1.01 (m, 6H); (ESI(+)) m/e 391 (M+H)+.


Table 18.


The following Examples were prepared essentially as described in Example 367, substituting the appropriate carboxylic acid in Example 367B.















Ex
Name

1H NMR

MS







368
N-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.07 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.87 (m,
m/e



ylmethyl)-4-{1-
3H), 7.52 (d, J = 1.2 Hz, 1H), 7.41 (m, 3H),
405 (M + H)1



[(2S)-2-
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.50 (d, J = 5.9 Hz,



methylbutanoyl]pyrrolidin-
2H), 3.90-3.66 (m, 1H), 3.63-3.20 (m,



3-
4H), 2.51 (m, 1H), 2.38-2.18 (m, 1H),



yl}benzamide
2.10-1.90 (m, 1H), 1.57 (m, 1H), 1.34 (m, 1H),




1.01 (m, 3H), 0.86 (m, 3H)


369
4-[1-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



(cyclopropylacetyl)pyrrolidin-
9.07 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (m,
m/e



3-yl]-N-
3H), 7.52 (d, J = 1.2 Hz, 1H), 7.42 (m, 3H),
403 (M + H)+



(imidazo[1,2-
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.50 (d, J = 5.9 Hz,



a]pyridin-7-
2H), 3.88 (m, 1H), 3.61 (m, 1H),



ylmethyl)benzamide
3.60-3.20 (m, 3H), 2.35-2.15 (m, 3H),




2.10-1.88 (m, 1H), 1.99 (m, 1H), 0.44 (m, 2H), 0.12 (m,




2H)


370
4-(1-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



benzoylpyrrolidin-
9.07 (m, 1H), 8.48 (t, J = 6.2 Hz, 1H), 7.88 (m,
m/e



3-yl)-N-
3H), 7.55 (m, 2H), 7.54-7.34 (m, 7H),
425 (M + H)+



(imidazo[1,2-
6.85 (m, 1H), 4.50 (m, 2H), 4.00 (m, 1H), 3.73 (m,



a]pyridin-7-
1H), 3.65-3.40 (m, 3H), 2.38-2.22 (m, 1H),



ylmethyl)benzamide
2.15-1.94 (m, 1H)


371
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.07 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.89 (m,
m/e



ylmethyl)-4-{1-
3H), 7.52 (d, J = 1.2 Hz, 1H), 7.41 (m, 3H),
421 (M + H)+



[(propan-2-
6.85 (dd, J = 7.0, 1.6 Hz, 1H), 4.51 (d, J = 5.9 Hz,



yloxy)acetyl]pyrrolidin-
2H), 4.05 (d, J = 4.5 Hz, 2H),



3-yl}benzamide
3.95-3.81 (m, 1H), 3.70-3.55 (m, 2H), 3.55-3.20 (m,




3H), 2.38-2.18 (m, 1H), 2.08-1.88 (m, 1H),




1.11 (m, 6H)


372
4-[1-(2-hydroxy-2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



methylpropanoyl)pyrrolidin-
9.07 (t, J = 6.0 Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H),
m/e



3-yl]-N-
7.88 (m, 3H), 7.52 (d, J = 1.2 Hz, 1H),
407 (M + H)+



(imidazo[1,2-
7.42 (m, 2H), 7.38 (m, 1H), 6.85 (dd, J = 7.0, 1.6 Hz,



a]pyridin-7-
1H), 5.15 (m, 1H), 4.50 (d, J = 5.9 Hz,



ylmethyl)benzamide
2H), 4.34 (m, 1H), 3.85-3.65 (m, 1H),




3.59 (m, 3H), 2.35-2.10 (m, 1H), 2.05-1.86 (m,




1H), 1.30 (m, 6H); )


373
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.07 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (m,
m/e



ylmethyl)-4-{1-
3H), 7.52 (s, 1H), 7.45-7.35 (m, 3H),
419 (M + H)+



[(2R)-
6.85 (d, J = 7.1 Hz, 1H), 4.55 (m, 1H), 4.50 (m,



tetrahydrofuran-2-
2H), 4.10-3.93 (m, 1H), 3.90-3.65 (m, 3H),



ylcarbonyl]pyrrolidin-
3.65-3.20 (m, 3H) 2.37-2.19 (m, 1H),



3-yl}benzamide
2.10-1.76 (m, 5H)


374
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.08 (m, 1H), 8.48 (m, 1H), 7.88 (m, 3H), 7.52 (s,
m/e



ylmethyl)-4-{1-
1H), 7.45-7.37 (m, 3H), 6.85 (dd, J = 7.0,
419 (M + H)+



[(2S)-
1.6 Hz, 1H), 4.55 (m, 1H), 4.50 (m, 2H),



tetrahydrofuran-2-
4.10-3.93 (m, 1H), 3.90-3.65 (m, 3H),



ylcarbonyl]pyrrolidin-
3.65-3.20 (m, 3H) 2.37-2.19 (m, 1H),



3-yl}benzamide
2.10-1.75 (m, 5H)


375
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.08 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.89 (m,
m/e



ylmethyl)-4-{1-
3H), 7.52 (s, 1H), 7.46 (m, 1H), 7.41 (m, 1H),
419 (M + H)+



[(3S)-
7.38 (m, 1H), 6.85 (d, J = 7.1 Hz, 1H),



tetrahydrofuran-3-
4.51 (m, 2H), 4.10-3.93 (m, 1H), 3.95-3.80 (m,



ylcarbonyl]pyrrolidin-
2H), 3.65-3.20 (m, 6H), 2.36-2.20 (m, 1H),



3-yl}benzamide
2.14-1.85 (m, 4H)


376
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.07 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (m,
m/e



ylmethyl)-4-[1-
3H), 7.51 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H),
433 (M + H)+



(tetrahydro-2H-
7.41 (m, 2H), 6.85 (m, 1H), 4.51 (d, J = 3.0 Hz,



pyran-4-
2H), 3.88 (m, 3H), 3.75 (m, .55 (m, 2H),



ylcarbonyl)pyrrolidin-
3.55-3.20 (m, 3H), 2.71 (m, 1H),



3-yl]benzamide
2.39-2.19 (m, 1H), 2.10-1.85 (m, 1H), 1.59 (m, 4H)


377
4-[1-(1,4-dioxan-2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



ylcarbonyl)pyrrolidin-
9.07 (m, 1H), 8.48 (d, J = 7.1 Hz, 1H), 7.89 (m,
m/e



3-yl]-N-
3H), 7.52 (s, 1H), 7.43 (m, 2H), 7.38 (s, 1H),
435 (M + H)+



(imidazo[1,2-
6.85 (d, J = 7.1 Hz, 1H), 4.51 (dd, J = 5.8, 2.9 Hz,



a]pyridin-7-
2H), 4.27 (m, 2H), 4.15-4.00 (m, 1H),



ylmethyl)benzamide
3.90-3.70 (m, 4H), 3.70-3.20 (m, 5H);




2.39-2.19 (m, 1H), 2.15-1.88 (m, 1H)


378
N-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm

(ESI(+))



a]pyridin-7-
9.07 (m, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (m,
m/e



ylmethyl)-4-[1-
3H), 7.52 (s, 1H), 7.42 (m, 2H), 7.38 (s, 1H),
447 (M + H)+



(tetrahydro-2H-
6.85 (d, J = 7.1 Hz, 1H), 4.51 (m, 2H),



pyran-4-
3.95 (m, 1H), 3.83 (m, 3H), 3.63 (m, 1H), 3.47 (m,



ylacetyl)pyrrolidin-
2H), 3.45-3.20 (m, 2H), 2.38-2.15 (m, 3H),



3-yl]benzamide
2.10-1.90 (m, 2H), 1.56 (m, 2H), 1.21 (m,




2H)


488
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-

431 (M + H)+



(thiophen-2-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


562
4-[1-(4-

(ESI(+))



fluorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

443 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


580
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[(2-

403 (M + H)+



methylcyclopropyl)carbonyl]pyrrolidin-



3-yl}benzamide


581
4-[1-

(ESI(+))



(cyclopentylacetyl)pyrrolidin-

m/e



3-yl]-N-

431 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


582
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(3-

419 (M + H)+



methylpentanoyl)pyrrolidin-



3-



yl]benzamide


583
4-[1-

(ESI(+))



(cyclopentylcarbonyl)pyrrolidin-

m/e



3-yl]-N-

417 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


584
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[(1-

403 (M + H)+



methylcyclopropyl)carbonyl]pyrrolidin-



3-yl}benzamide


585
4-[1-(2,2-

(ESI(+))



dimethylpropanoyl)pyrrolidin-

m/e



3-yl]-N-

405 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


586
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(1,3-

432 (M + H)+



thiazol-5-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


587
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(2-

455 (M + H)+



methoxybenzoyl)pyrrolidin-



3-



yl]benzamide


588
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(1,3-

432 (M + H)+



thiazol-4-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


589
4-[1-(2-

(ESI(+))



fluorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

443 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


590
4-[1-(furan-2-

(ESI(+))



ylcarbonyl)pyrrolidin-

m/e



3-yl]-N-

415 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


591
4-[1-(3-

(ESI(+))



fluorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

443 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


592
4-[1-(2,4-

(ESI(+))



difluorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

461 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


593
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[(1-

429 (M + H)+



methyl-1H-pyrazol-



3-



yl)carbonyl]pyrrolidin-



3-yl}benzamide


594
4-[1-(2-

(ESI(+))



chlorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

459 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


595
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(2-

439 (M + H)+



methylbenzoyl)pyrrolidin-



3-



yl]benzamide


596
4-[1-(4-

(ESI(+))



chlorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

459 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


597
4-[1-(3-

(ESI(+))



chlorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

459 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


598
4-[1-(2,2-

(ESI(+))



dimethylbutanoyl)pyrrolidin-

m/e



3-yl]-N-

419 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


599
4-[1-(3,5-

(ESI(+))



difluorobenzoyl)pyrrolidin-

m/e



3-yl]-N-

461 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


600
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(4-

439 (M + H)+



methylbenzoyl)pyrrolidin-



3-



yl]benzamide


601
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(3-

405 (M + H)+



methylbutanoyl)pyrrolidin-



3-



yl]benzamide


602
4-[1-(3,3-

(ESI(+))



dimethylbutanoyl)pyrrolidin-

m/e



3-yl]-N-

419 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


603
4-[1-(3-

(ESI(+))



cyanobenzoyl)pyrrolidin-

m/e



3-yl]-N-

450 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


604
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(3-

455 (M + H)+



methoxybenzoyl)pyrrolidin-



3-



yl]benzamide


605
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(4-

455 (M + H)+



methoxybenzoyl)pyrrolidin-



3-



yl]benzamide


606
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[(1-

428 (M + H)+



methyl-1H-pyrrol-2-



yl)carbonyl]pyrrolidin-



3-yl}benzamide


607
4-[1-

(ESI(+))



(cyclohexylacetyl)pyrrolidin-

m/e



3-yl]-N-

445 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


608
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-

426 (M + H)+



(pyridin-4-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


609
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-

426 (M + H)+



(pyridin-3-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


610
4-[1-

(ESI(+))



(cyclohexylcarbonyl)pyrrolidin-

m/e



3-yl]-N-

431 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


611
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-

426 (M + H)+



(pyridin-2-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


612
4-[1-(furan-3-

(ESI(+))



ylcarbonyl)pyrrolidin-

m/e



3-yl]-N-

415 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


613
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(1,3-

432 (M + H)+



thiazol-2-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


614
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[(1-

445 (M + H)+



methylcyclohexyl)carbonyl]pyrrolidin-



3-yl}benzamide


615
4-[1-(2,3-

(ESI(+))



dimethylbutanoyl)pyrrolidin-

m/e



3-yl]-N-

419 (M + H)+



(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide


616
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(3-

439 (M + H)+



methylbenzoyl)pyrrolidin-



3-



yl]benzamide


617
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-

431 (M + H)+



(thiophen-3-



ylcarbonyl)pyrrolidin-



3-yl]benzamide


618
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[3-

509 (M + H)+



(trifluoromethoxy)benzoyl]pyrrolidin-



3-



yl}benzamide


619
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[(3-

445 (M + H)+



methylthiophen-2-



yl)carbonyl]pyrrolidin-



3-yl}benzamide


620
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-{1-[3-

493 (M + H)+



(trifluoromethyl)benzoyl]pyrrolidin-



3-



yl}benzamide


731
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-

439 (M + H)+



(phenylacetyl)pyrrolidin-



3-yl]benzamide


732
N-(imidazo[1,2-

(ESI(+))



a]pyridin-7-

m/e



ylmethyl)-4-[1-(2-

467 (M + H)+



methyl-2-



phenylpropanoyl)pyrrolidin-



3-



yl]benzamide


733
4-{1-

(ESI(+))



[difluoro(phenyl)acetyl]pyrrolidin-

m/e



3-yl}-

475 (M + H)+



N-(imidazo[1,2-



a]pyridin-7-



ylmethyl)benzamide









Example 379
1-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
Example 379A
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(pyrrolidin-3-yl)phenyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 379B
1-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(pyrrolidin-3-yl)phenyl)urea for 3-methylbutan-1-amine and acetic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J=6.4 Hz, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s, 1H), 7.37 (m, 3H), 7.16 (m, 2H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.69 (m, 1H), 4.33 (d, J=6.0 Hz, 2H), 3.89-3.73 (m, 1H), 3.65-3.45 (m, 3H), 3.10 (m, 1H), 2.29-2.11 (m, 1H), 2.00-1.80 (m, 1H), 1.91 (s, 3H); (ESI(+)) m/e 378 (M+H)+.


Table 19.


The following Examples were prepared essentially as described in Example 379, substituting the appropriate carboxylic acid in Example 379B.















Ex
Name

1H NMR

MS







380
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 6.5

(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 406



ylmethyl)-3-{4-[1-(2-
1H), 7.36 (m, 3H), 7.16 (m, 2H), 6.83 (d, J = 7.1 Hz,
(M + H)+



methylpropanoyl)
1H), 6.70 (m, 1H), 4.33 (d, J = 6.0 Hz, 2H), 3.80-3.65




pyrrolidin-3-
(m, 1H), 3.60-3.48 (m, 1H), 3.45-3.20 (m, 2H), 3.13




yl]phenyl}urea
(m, 1H), 2.68 (m, 1H), 2.30-2.10 (m, 1H), 2.05-1.80





(m, 1H), 1.00 (m, 6H)



381
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 6.5

(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.52 (s,
m/e 420



ylmethyl)-3-(4-{1-
1H), 7.37 (m, 3H), 7.17 (m, 2H), 6.83 (dd, J = 7.0, 1.6
(M + H)+



[(2S)-2-methyl-
Hz, 1H), 6.69 (t, J = 6.0 Hz, 1H), 4.33 (d, J = 6.0 Hz,




butanoyl]pyrrolidin-3-
2H), 3.95-3.75 (m, 1H), 3.70 -3.45 (m, 2H), 3.45-3.20




yl}phenyl)urea
(m, 1H), 3.20 (m, 1H), 2.30-2.11 (m, 1H), 2.05-1.80





(m, 1H), 1.55 (m, 1H), 1.25 (m, 2H), 0.96 (m, 3H), 0.87





(m, 3H)



382
1-{4-[1-(cyclopropyl-
-1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 4.1
(ESI(+))



acetyl)pyrrolidin-3-
Hz, 1H), 8.49 (d, J = 7.0 Hz, 1H), 7.89 (s, 1H), 7.52 (s,
m/e 418



yl]phenyl}-3-
1H), 7.37 (m, 3H), 7.16 (m, 2H), 6.84 (d, J = 7.1 Hz,
(M + H)+



(imidazo[1,2-a]
1H), 6.69 (t, J = 6.0 Hz, 1H), 4.33 (d, J = 6.0 Hz, 2H),




pyridin-7-
3.80 (m, 1H), 3.58 (m, 1H), 3.45 (m, 1H), 3.40-3.20 (m,




ylmethyl)urea
1H), 3.12 (m, 1H), 2.27-2.11 (m, 3H), 1.99-1.81 (m,





1H), 0.98 (m, 1H), 0.44 (m, 2H), 0.11 (m, 2H)



383
1-[4-(1-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (m, 1H),

(ESI(+))



benzoylpyrrolidin-3-
8.48 (d, J = 6.1 Hz, 1H), 7.88 (d, J = 3.0 Hz, 1H), 7.53
m/e 440



yl)phenyl]-3-
(m, 3H), 7.50-7.35 (m, 5H), 7.34 (d, 1H), 7.20 (d, J =
(M + H)+



(imidazo[1,2-
8.2 Hz, 1H), 7.13 (d, J = 8.2 Hz, 1H), 6.83 (m, 1H),




a]pyridin-7-
6.68 (m, 1H), 4.33 (d, J = 14.1 Hz, 2H), 3.68 (m, 1H),




ylmethyl)urea
3.60-3.45 (m, 2H), 3.40-3.20 (m, 2H), 2.29-2.13 (m,





1H) 2.07-1.90 (m, 1H)



384
1-(imidazo[1,2-
-1H NMR (500 MHz, DMSO-d6) δ ppm 8.63 (d, J = 6.0
(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 436



ylmethyl)-3-(4-
1H), 7.37 (m, 3H), 7.16 (m, 2H), 6.83 (dd, J = 7.0, 1.6
(M + H)+



{1-[(propan-2-
Hz, 1H), 6.70 (m, 1H), 4.33 (d, J = 6.0 Hz, 2H), 4.03 (d,




yloxy)acetyl]
J = 5.4 Hz, 2H), 3.90-3.74 (m, 1H), 3.68-3.52 (m, 2H),




pyrrolidin-3-
3.47 (m, 1H), 3.40-3.20 (m, 1H), 3.16 (m, 1H), 2.29-




yl}phenyl)urea
2.11 (m, 1H), 2.00-1.73 (m, 1H), 1.10 (m, 6H)



385
1-{4-[1-(2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.65 (d, J = 6.0

(ESI(+))



hydroxy-2-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 422



methylpropanoyl)
1H), 7.37 (m, 3H), 7.16 (m, 2H), 6.83 (dd, J = 7.0, 1.6
(M + H)+



pyrrolidin-3-
Hz, 1H), 6.73 (m, 1H), 5.18 (bs, 1H), 4.33 (d, J = 6.0




yl]phenyl}-3-
Hz, 2H), 4.28 (m, 1H), 3.80-3.60 (m, 1H), 3.60-3.10 (m,




(imidazo[1,2-
3H), 2.25-2.08 (m, 1H), 1.97-1.73 (m, 1H), 1.30 (m, 6H)




a]pyridin-7-





ylmethyl)urea




386
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 5.7

(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 434



ylmethyl)-3-(4-
1H), 7.37 (m, 3H), 7.16 (m, 2H), 6.83 (d, J = 6.2 Hz,
(M + H)+



{1-[(2R)-
1H), 6.69 (t, J = 6.0 Hz, 1H), 4.53 (m, 1H), 4.33 (d, J =




tetrahydrofuran-2-
6.0 Hz, 2H), 3.85-3.64 (m, 3H), 3.63-3.45 (m, 1H), 3.45-




ylcarbonyl]
3.20 (m, 2H), 3.16 (m, 1H), 2.29-2.10 (m, 1H), 2.08-




pyrrolidin-3-
1.92 (m, 2H), 1.91-1.73 (m, 3H)




yl}phenyl)urea




387
1-(imidazo[1,2-
-1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 5.6
(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 434



ylmethyl)-3-(4-
1H), 7.36 (m, 3H), 7.16 (m, 2H), 6.83 (dd, J = 7.0, 1.6
(M + H)+



{1-[(2S)-
Hz, 1H), 6.69 (t, J = 6.0 Hz, 1H), 4.53 (m, 1H), 4.33 (d,




tetrahydrofuran-
J = 6.0 Hz, 2H), 3.84-3.64 (m, 3H), 3.63-3.45 (m, 1H),




2-ylcarbonyl]
3.45-3.20 (m, 2H), 3.16 (m, 1H), 2.29-2.10 (m, 1H),




pyrrolidin-3-
2.05-1.85 (m, 5H)




yl}phenyl)urea




388
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.63 (d, J = 6.7

(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.52 (s,
m/e 434



ylmethyl)-3-(4-{1-
1H), 7.37 (m, 3H), 7.17 (m, 2H), 6.83 (dd, J = 7.0, 1.6
(M + H)+



[(3S)-tetrahydrofuran-
Hz, 1H), 6.70 (m, 1H), 4.33 (d, J = 6.0 Hz, 2H), 3.97-




3-ylcarbonyl]
3.84 (m, 2H), 3.80-3.63 (m, 4H), 3.62-3.46 (m, 1H),




pyrrolidin-3-
3.45-3.10 (m, 3H), 2.29-2.10 (m, 1H), 2.09-1.83 (m, 3H)




yl}phenyl)urea




389
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 7.5

(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 448



ylmethyl)-3-{4-
1H), 7.36 (m, 3H), 7.16 (m, 2H), 6.83 (d, J = 7.1 Hz,
(M + H)+



[1-(tetrahydro-2H-
1H), 6.69 (t, J = 6.0 Hz, 1H), 4.33 (d, J = 6.0 Hz, 2H),




pyran-4-ylcarbonyl)
3.90-3.70 (m, 3H), 3.55 (m, 1H), 3.45-3.20 (m, 3H),




pyrrolidin-3-
3.15 (m, 1H), 2.70 (m, 1H), 2.28-2.11 (m, 1H), 2.00-




yl]phenyl}urea
1.82 (m, 1H), 1.57 (m, 4H)



390
1-{4-[(1,4-dioxan-2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.62 (d, J = 7.5

(ESI(+))



ylcarbonyl)
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 450



pyrrolidin-3-
1H), 7.37 (m, 3H), 7.16 (m, 2H), 6.83 (d, J = 7.1 Hz,
(M + H)+



yl]phenyl}-
1H), 6.70 (t, J = 6.0 Hz, 1H), 4.33 (d, J = 6.0 Hz, 2H),




3-(imidazo[1,2-
4.25 (m, 1H), 3.85-3.70 (m, 3H), 3.70-3.60 (m, 2H),




a]pyridin-7-
3.60-3.45 (m, 3H), 3.45-3.15 (m, 3H), 2.28-2.11 (m,




ylmethyl)urea
1H), 2.00-1.80 (m, 1H)



391
1-(imidazo[1,2-
-1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (d, J = 5.5
(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s,
m/e 462



ylmethyl)-3-{4-
1H), 7.36 (m, 3H), 7.16 (m, 2H), 6.83 (dd, J = 7.0, 1.6
(M + H)+



[1-(tetrahydro-
Hz, 1H), 6.69 (t, J = 6.0 Hz, 1H), 4.33 (d, J = 5.9 Hz,




2H-pyran-4-ylacetyl)
2H), 3.90-3.72 (m, 3H), 3.67-3.40 (m, 2H), 3.27-3.08




pyrrolidin-3-yl]
(m, 2H), 3.14 (m, 1H), 2.28-2.10 (m, 3H), 2.00-1.80 (m,




phenyl}urea
3H), 1.59 (m, 2H), 1.17 (m, 2H)



392
1-(imidazo[1,2-
-1H NMR (400 MHz, DMSO-d6) δ ppm 8.65 (d, J = 6.1
(ESI(+))



a]pyridin-7-
Hz, 1H), 8.48 (d, J = 6.9 Hz, 1H), 7.88 (s, 1H), 7.51 (d,
m/e 463



ylmethyl)-3-{4-
J = 1.2 Hz, 1H), 736 (m, 3H), 7.16 (m, 2H), 6.83 (dd, J =
(M + H)+



[1-(morpholin-
6.9, 1.7 Hz, 1H), 6.72 (td, J = 6.0, 2.3 Hz, 1H), 4.33 (d,




4-ylacetyl)
J = 5.9 Hz, 2H), 3.74 (m, 1H), 3.55 (m, 4H), 3.45-3.20




pyrrolidin-3-yl]
(m, 2H), 3.17 (s, 2H), 3.13-3.03 (m, 2H), 2.44 (m, 4H),




phenyl}urea
2.30-2.10 (m, 1H), 2.00-1.80 (m, 1H)









Example 393
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide
Example 393A
methyl 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(methoxycarbonyl)benzoic acid for 4-nitrobenzoic acid.


Example 393B
4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid

The title compound was prepared as described in Example 4B, substituting methyl 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 393C
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N′-(3-methylbutyl)benzene-1,4-dicarboxamide

The title compound was prepared as described in Example 1A, substituting 3-methylbutan-1-amine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.25-9.11 (m, 1H), 8.57-8.37 (m, 2H), 8.04-7.81 (m, 5H), 7.51 (t, J=2.6 Hz, 1H), 7.41 (t, J=2.9 Hz, 1H), 6.87 (dd, J=7.0, 1.7 Hz, 1H), 4.58-4.38 (m, 2H), 3.29-3.25 (m, 2H), 1.71-1.56 (m, 1H), 1.53-1.31 (m, 2H), 0.91 (d, J=6.5 Hz, 6H); MS (ESI(+)) m/e 365 (M+H)+.


Example 394
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-N′-[(3S)-tetrahydrofuran-3-ylmethyl]benzene-1,4-dicarboxamide

The title compound was prepared as described in Example 1A, substituting (5)-(tetrahydrofuran-3-yl)methanamine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.21 (t, J=5.9 Hz, 1H), 8.69 (t, J=5.7 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.07-7.71 (m, 5H), 7.52 (d, J=1.2 Hz, 1H), 7.41 (s, 1H), 6.87 (dd, J=7.0, 1.7 Hz, 1H), 4.52 (d, J=5.9 Hz, 2H), 3.80-3.56 (m, 4H), 3.48 (dd, J=8.5, 5.2 Hz, 1H), 2.02-1.87 (m, 1H), 1.68-1.53 (m, 1H), 1.32-1.00 (m, 2H); MS (ESI(+)) m/e 379 (M+H)+.


Example 396
4-{[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]amino}-N-(tetrahydro-2H-pyran-2-ylmethyl)benzamide

A solution of 4-(3-imidazo[1,2-a]pyridin-6-ylureido)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide (0.016 g, 0.041 mmol) in chloroform (0.813 ml) was treated with N-chlorosuccinimide (5.70 mg, 0.043 mmol) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under a stream of nitrogen and purified using normal phase chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.11 (s, 1H), 9.02 (s, 1H), 8.89-8.85 (m, 1H), 8.35 (t, J=5.8 Hz, 1H), 7.85-7.79 (m, 2H), 7.69-7.60 (m, 2H), 7.58-7.52 (m, 2H), 7.19 (dd, J=9.5, 2.0 Hz, 1H), 3.91-3.83 (m, 1H), 3.46-3.19 (m, 4H), 1.80-1.73 (m, 1H), 1.66-1.57 (m, 1H), 1.49-1.36 (m, 3H), 1.26-1.09 (m, 1H); MS (ESI(+)) m/e 428 (M+H)+.


Example 398
N-[(3-chloroimidazo[1,2-a]pyridin-6-yl)methyl]-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide

The title compound was prepared as described in Example 396, substituting N-[(3-imidazo[1,2-a]pyridin-6-yl)methyl]-4-[(tetrahydrofuran-3-ylacetyl)amino]benzamide for 4-(3-imidazo[1,2-a]pyridin-6-ylureido)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.15 (s, 1H), 8.95 (t, J=5.8 Hz, 1H), 8.30-8.25 (m, 1H), 7.87-7.80 (m, 2H), 7.71-7.59 (m, 4H), 7.35 (dd, J=9.3, 1.7 Hz, 1H), 4.54 (d, J=5.8 Hz, 2H), 3.86-3.58 (m, 3H), 3.38-3.30 (m, 1H), 2.62-2.52 (m, 1H), 2.47-2.39 (m, 2H), 2.10-1.95 (m, 1H), 1.62-1.46 (m, 1H); MS (ESI(+)) m/e 413 (M+H)+.


Example 399
5-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 399A
5-(4-hydroxytetrahydro-2H-pyran-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 324A, substituting dihydro-2H-pyran-4(3H)-one for N-(oxetan-3-ylidene)propane-2-sulfinamide.


Example 399B
5-(4-hydroxytetrahydro-2H-pyran-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(4-hydroxytetrahydro-2H-pyran-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.99 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.66 (d, J=3.7 Hz, 1H), 7.52 (s, 1H), 7.37 (s, 1H), 7.02 (d, J=3.7 Hz, 1H), 6.83 (dd, J=7.0, 1.5 Hz, 1H), 5.67 (s, 1H), 4.46 (d, J=6.1 Hz, 2H), 3.63-3.77 (m, 4H), 1.89-2.04 (m, 2H), 1.69 (d, J=11.9 Hz, 2H); MS (ESI(+)) m/e 358 (M+H)+.


Example 400
5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 400A
5-(1-(tert-butoxycarbonyl)-3-hydroxyazetidin-3-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 324A, substituting tert-butyl 3-oxoazetidine-1-carboxylate for N-(oxetan-3-ylidene)propane-2-sulfinamide.


Example 400B
tert-butyl 3-hydroxy-3-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(1-(tert-butoxycarbonyl)-3-hydroxyazetidin-3-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 400C
5-(3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-hydroxy-3-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)azetidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 400D
5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.06 (t, J=6.0 Hz, 1H), 8.49 (d, J=7.1 Hz, 1H), 7.89 (s, 1H), 7.72 (d, J=3.6 Hz, 1H), 7.52 (s, 1H), 7.38 (s, 1H), 7.18 (d, J=3.6 Hz, 1H), 6.90 (s, 1H), 6.83 (dd, J=6.9, 1.4 Hz, 1H), 4.47 (d, J=6.0 Hz, 2H), 4.41 (d, J=9.1 Hz, 1H), 4.32 (d, J=9.1 Hz, 1H), 4.05 (dd, J=17.5, 9.9 Hz, 2H), 2.46-2.57 (m, 1H), 1.00 (d, J=7.1 Hz, 6H); MS (ESI(+)) m/e 399 (M+H)+.


Example 401
5-(1-benzoyl-3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.05 (t, J=5.8 Hz, 1H), 8.48 (d, J=6.1 Hz, 1H), 7.88 (s, 1H), 7.73 (d, J=3.7 Hz, 1H), 7.66-7.71 (m, 2H), 7.43-7.54 (m, 4H), 7.38 (d, J=1.0 Hz, 1H), 7.26 (d, J=3.7 Hz, 1H), 6.93 (s, 1H), 6.83 (dd, J=7.1, 1.7 Hz, 1H), 4.46 (d, J=6.1 Hz, 2H), 4.23-4.63 (br. m, 4H); MS (ESI(+)) m/e 433 (M+H)+.


Example 402
tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)azetidin-3-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.09 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.91 (m, 3H), 7.52 (d, J=1.2 Hz, 1H), 7.45 (m, 2H), 7.38 (s, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.26 (m, 2H), 3.87 (m, 3H), 1.41 (s, 9H); (ESI(+)) m/e 407 (M+H)+.


Example 403
tert-butyl 4-hydroxy-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate
Example 403A
5-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 324A, substituting tert-butyl 3-oxopiperidine-1-carboxylate for N-(oxetan-3-ylidene)propane-2-sulfinamide.


Example 403B
tert-butyl 4-hydroxy-4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.98 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.65 (d, J=4.1 Hz, 1H), 7.51 (d, J=1.0 Hz, 1H), 7.37 (s, 1H), 7.01 (d, J=3.7 Hz, 1H), 6.83 (dd, J=7.0, 1.5 Hz, 1H), 5.72 (s, 1H), 4.46 (d, J=5.8 Hz, 2H), 3.75-3.86 (m, 2H), 1.71-1.86 (m, 2H), 1.41 (s, 9H), 1.21-1.30 (m, 2H), 0.94 (d, J=5.8 Hz, 2H); MS (ESI(+)) m/e 457 (M+H)+.


Example 404
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[5-(piperidin-1-ylcarbonyl)-1,3-thiazol-2-yl]urea
Example 404A
ethyl 2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylate

The title compound was prepared as described in Example 1C, substituting ethyl 2-aminothiazole-5-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 404B
2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylic acid

The title compound was prepared as described in Example 4B, substituting ethyl 2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 404C
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[5-(piperidin-1-ylcarbonyl)-1,3-thiazol-2-yl]urea

The title compound was prepared as described in Example 1A, substituting piperidine for 3-methylbutan-1-amine and 2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.91 (s, 1H), 8.49 (d, J=7.1 Hz, 1H), 7.89 (s, 1H), 7.62 (s, 1H), 7.52 (d, J=0.8 Hz, 1H), 7.39 (s, 1H), 7.11-7.18 (m, 1H), 6.83 (dd, J=6.9, 1.4 Hz, 1H), 4.39 (d, J=6.0 Hz, 2H), 3.54-3.61 (m, 4H), 1.47-1.67 (m, 6H); MS (ESI(+)) m/e 385 (M+H)+.


Example 405
5-{3-hydroxy-1-[(2S)-2-methylbutanoyl]azetidin-3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.06 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.72 (d, J=4.1 Hz, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.38 (s, 1H), 7.16 (dd, J=7.0, 3.9 Hz, 1H), 6.89 (s, 1H), 6.83 (dd, J=7.0, 1.5 Hz, 1H), 4.46 (d, J=6.1 Hz, 2H), 4.35-4.42 (m, 1H), 4.32 (d, J=8.8 Hz, 1H), 4.09 (dd, J=10.5, 4.4 Hz, 1H), 4.03 (d, J=10.2 Hz, 1H), 2.25-2.38 (m, 1H), 1.49 (s, 1H), 1.23-1.38 (m, 1H), 0.99 (d, J=6.8 Hz, 3H), 0.80-0.88 (m, 3H); MS (ESI(+)) m/e 413 (M+H)+.


Example 406
5-[3-hydroxy-1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-hydroxyazetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 2-(tetrahydro-2H-pyran-4-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (t, J=6.0 Hz, 1H), 8.49 (d, J=7.0 Hz, 1H), 7.89 (s, 1H), 7.72 (d, J=4.0 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.38 (s, 1H), 7.18 (d, J=4.0 Hz, 1H), 6.89 (s, 1H), 6.83 (dd, J=7.0, 1.5 Hz, 1H), 4.47 (d, J=5.8 Hz, 2H), 4.37 (d, J=9.2 Hz, 1H), 4.26-4.40 (m, 2H), 4.05-4.11 (m, 1H), 4.00-4.10 (m, 2H), 3.78-3.84 (m, 2H), 2.04-2.07 (m, 2H), 1.85-1.97 (m, 1H), 1.53-1.62 (m, 2H), 1.15-1.28 (m, 2H); MS (ESI(+)) m/e 455 (M+H)+.


Example 407
2-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}-N-(3-methylbutyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting 3-methylbutan-1-amine for 3-methylbutan-1-amine and 2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.49 (d, J=7.8 Hz, 1H), 8.21 (t, J=5.9 Hz, 1H), 7.88-7.89 (m, J=1.4 Hz, 1H), 7.87 (s, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.39 (s, 1H), 7.18 (t, J=5.8 Hz, 1H), 6.83 (dd, J=6.8, 1.7 Hz, 1H), 4.38 (d, J=6.1 Hz, 2H), 3.16-3.25 (m, 2H), 1.52-1.67 (m, 1H), 1.38 (q, J=6.9 Hz, 2H), 0.83-0.91 (m, 7H); MS (ESI(+)) m/e 387 (M+H)+.


Example 408
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(3-{[(2S)-2-methylbutanoyl]amino}oxetan-3-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(3-aminooxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.11 (s, 1H), 9.05 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.8 Hz, 1H), 7.88 (s, 1H), 7.71 (d, J=3.7 Hz, 1H), 7.52 (s, 1H), 7.38 (s, 1H), 7.22 (d, J=3.7 Hz, 1H), 6.83 (dd, J=7.1, 1.7 Hz, 1H), 4.77-4.83 (m, 2H), 4.72 (dd, J=6.4, 4.4 Hz, 2H), 4.46 (d, J=5.8 Hz, 2H), 2.19-2.29 (m, 1H), 1.46-1.66 (m, 1H), 1.26-1.43 (m, 1H), 1.03 (d, J=6.8 Hz, 3H), 0.85 (t, J=7.3 Hz, 3H); MS (ESI(+)) m/e 413 (M+H)+.


Example 409
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1-[1-(3-methylbutanoyl)piperidin-4-yl]-1H-pyrazole-3-carboxamide
Example 409A
1-(4-hydroxypiperidin-1-yl)-3-methylbutan-1-one

The title compound was prepared as described in Example 52A, substituting 3-methylbutanoyl chloride for 2-cyclopentylacetyl chloride and piperidin-4-ol for methyl 4-aminobenzoate.


Example 409B
ethyl 1-(1-(3-methylbutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxylate

A solution of 1-(hydroxypiperidin-1-yl)-3-methylbutan-1-one (793 mg, 4.28 mmol), ethyl 1H-pyrazole-4-carboxylate (500 mg, 3.57 mmol) and cyanomethylenetributylphosphorane (1.03 g, 4.28 mmol) in toluene (20 ml) was stirred overnight at 85° C. The solvent was removed and the crude mixture was purified by normal phase chromatography to give the title compound.


Example 409C
1-(1-(3-methylbutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxylic acid

The title compound was prepared as described in Example 4B, substituting ethyl 1-(1-(3-methylbutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxylate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 409D
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1-[1-(3-methylbutanoyl)piperidin-4-yl]-1H-pyrazole-3-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 1-(1-(3-methylbutanoyl)piperidin-4-yl)-1H-pyrazole-3-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.10 (t, J=6.0 Hz, 1H), 8.50 (dd, J=7.0, 0.9 Hz, 1H), 7.93-7.86 (m, 1H), 7.57-7.47 (m, 2H), 7.41 (s, 1H), 6.92 (d, J=2.0 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 5.45-5.28 (m, 1H), 4.57-4.43 (m, 3H), 3.99 (d, J=14.0 Hz, 1H), 3.20-3.03 (m, 1H), 2.70-2.53 (m, 1H), 2.32-2.11 (m, 3H), 2.09-1.68 (m, 4H), 0.91 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 408 (M+H).


Example 424
1-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
Example 424A
tert-butyl 3-(4-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)phenoxy)azetidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 3-(4-aminophenoxy)azetidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine.


Example 424B
1-(4-(azetidin-3-yloxy)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-(4-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)phenoxy)azetidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 424C
1-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(4-(azetidin-3-yloxy)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.50 (m, 2H), 7.88 (s, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (m, 1H), 7.33 (m, 2H), 6.83 (dd, J=6.9, 1.6 Hz, 1H), 6.74 (m, 2H), 6.63 (t, J=6.0 Hz, 1H), 4.93 (m, 1H), 4.51 (m, 1H), 4.32 (d, J=6.0 Hz, 2H), 4.24 (m, 1H), 4.04 (dd, J=9.6, 4.1 Hz, 1H), 3.72 (dd, J=10.5, 4.0 Hz, 1H), 1.78 (s, 3H); (ESI(+)) m/e 380 (M+H)+.


Table 20.


The following Examples were prepared essentially as described in Example 424, substituting the appropriate carboxylic acid in Example 424C.















Ex
Name

1H NMR

MS







425
1-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,

(ESI(+))



a]pyridin-7-
2H), 7.88 (s, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.37
m/e 408



ylmethyl)-3-(4-
(m, 1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9, 1.7 Hz,
(M + H)+



{[1-(2-
1H), 6.75 (m, 2H), 6.63 (t, J = 6.0 Hz, 1H), 4.95




methylpropanoyl)
(m, 1H), 4.57 (dd, J = 9.4, 6.4 Hz, 1H), 4.32 (d, J =




azetidin-3-
6.0 Hz, 2H), 4.25 (dd, J = 10.5, 6.5 Hz, 1H),




yl]oxy}phenyl)
4.08 (dd, J = 9.4, 3.9 Hz, 1H), 3.73 (dd, J = 10.5,




urea
4.0 Hz, 1H), 2.47 (m, 1H), 0.97 (m, 6H)



426
1-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,

(ESI(+))



a]pyridin-7-
2H), 7.88 (d, J = 1.1 Hz, 1H), 7.51 (d, J = 1.2 Hz,
m/e 422



ylmethyl)-3-[4-
1H), 7.37 (m, 1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9,
(M + H)+



({1-[(2S)-2-
1.6 Hz, 1H), 6.75 (m, 2H), 6.64 (t, J = 6.0 Hz,




methylbutanoyl]
1H), 4.95 (m, 1H), 4.56 (dd, J = 9.4, 6.5 Hz, 1H),




azetidin-3-
4.32 (d, J = 6.0 Hz, 2H), 4.26 (m, 1H), 4.08 (m,




yl}oxy)phenyl]
1H), 3.74 (m, 1H), 2.28 (m, 1H), 1.47 (m, 1H),




urea
1.28 (m, 1H), 0.95 (m, 3H), 0.81 (m, 3H)



427
1-(4-{[1-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,

(ESI(+))



(cyclopropyl-
2H), 7.90 (s, 1H), 7.54 (d, J = 1.2 Hz, 1H), 7.39
m/e 420



acetyl)azetidin-3-
(s, 1H), 7.33 (m, 2H), 6.86 (dd, J = 7.0, 1.6 Hz,
(M + H)+



yl]oxy}phenyl)-
1H), 6.74 (m, 2H), 6.64 (t, J = 6.0 Hz, 1H), 4.94




3-(imidazo[1,2-
(m, 1H), 4.50 (dd, J = 9.6, 6.6 Hz, 1H), 4.33 (d, J =




a]pyridin-7-
6.0 Hz, 2H), 4.26 (dd, J = 10.5, 6.5 Hz, 1H),




ylmethyl)urea
4.03 (dd, J = 9.4, 3.9 Hz, 1H), 3.74 (dd, J = 10.5,





3.9 Hz, 1H), 2.02 (d, J = 6.8 Hz, 2H), 0.92 (m,





1H), 0.43 (m, 2H), 0.10 (m, 2H)



428
1-{4-[(1-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,

(ESI(+))



benzoylazetidin-3-
2H), 7.88 (s, 1H), 7.65 (m, 2H), 7.52 (m, 2H),
m/e 442



yl)oxy]phenyl}-
7.45 (m, 2H), 7.37 (m, 1H), 7.33 (m, 2H), 6.83
(M + H)+



3-(imidazo[1,2-
(dd, J = 6.9, 1.6 Hz, 1H), 6.75 (m, 2H), 6.63 (t, J =




a]pyridin-7-
6.0 Hz, 1H), 5.00 (m, 1H), 4.67 (m, 1H), 4.51




ylmethyl)urea
(m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 4.26 (m, 1H),





3.97 (m, 1H)



429
1-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,

(ESI(+))



a]pyridin-7-
2H), 7.88 (s, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.37
m/e 438



ylmethyl)-3-[4-
(s, 1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9, 1.6 Hz,
(M + H)+



({1-[(propan-2-
1H), 6.74 (m, 2H), 6.64 (t, J = 6.0 Hz, 1H), 4.96




yloxy)acetyl]
(m, 1H), 4.60 (dd, J = 10.1, 6.4 Hz, 1H), 4.30 (m,




azetidin-3-
3H), 4.11 (dd, J = 10.1, 3.9 Hz, 1H), 3.94 (s, 2H),




yl}oxy)phenyl]
3.77 (dd, J = 10.7, 3.8 Hz, 1H), 3.58 (m, 1H), 1.09




urea
d, J = 6.1 Hz, 6H)



430
1-(4-{[1-(2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (m,

(ESI(+))



hydroxy-2-
2H), 7.88 (s, 1H), 7.51 (s, 1H), 7.38 (s, 1H), 7.33
m/e 424



methylpropanoyl)
(m, 2H), 6.83 (dd, J = 6.9, 1.6 Hz, 1H), 6.74 (m,
(M + H)+



azetidin-3-
2H), 6.63 (t, J = 6.0 Hz, 1H), 5.13 (s, 1H), 4.91




yl]oxy}phenyl)-
(m, 1H), 4.78 (m, 1H), 4.32 (d, J = 6.0 Hz, 3H),




3-(imidazo[1,2-
4.26 (m, 1H), 3.73 (m, 1H), 1.25 (s, 6H)




a]pyridin-7-





ylmethyl)urea




431
1-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,

(ESI(+))



a]pyridin-7-
2H), 7.88 (s, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.37
m/e 436



ylmethyl)-3-[4-
(s, 1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9, 1.6 Hz,
(M + H)+



({1-[(2R)-
1H), 6.74 (m, 2H), 6.63 (t, J = 6.0 Hz, 1H), 4.95




tetrahydrofuran-
(m, 1H), 4.66 (m, 1H), 4.31 (m, 4H), 4.13 (m,




2-ylcarbonyl]
1H), 3.75 (m, 3H), 2.03 (m, 1H), 1.93 (m, 1H),




azetidin-3-yl}
1.81 (m, 2H)




oxy)phenyl]urea




432
1-(imidazo[1,2-
1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (m,
(ESI(+))



a]pyridin-7-
2H), 7.88 (s, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.37
m/e 436



ylmethyl)-3-[4-
(s, 1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9, 1.6 Hz,
(M + H)+



({1-[(2S)-
1H), 6.74 (m, 2H), 6.64 (t, J = 6.0 Hz, 1H), 4.95




tetrahydro-
(m, 1H), 4.66 (m, 1H), 4.3123 (m, 4H), 4.13 (m,




furan2-
1H), 3.75 (m, 3H), 2.03 (m, 1H), 1.93 (m, 1H),




ylcarbonyl]
1.81 (m, 2H)




azetidin-3-





yl}oxy)phenyl]urea




433
1-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (m,

(ESI(+))



a]pyridin-7-
2H), 7.88 (d, J = 1.1 Hz, 1H), 7.51 (d, J = 1.2 Hz,
m/e 450



ylmethyl)-3-(4-
1H), 7.37 (s, 1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9,
(M + H)+



{[1-(tetrahydro-
1.7 Hz, 1H), 6.74 (m, 2H), 6.64 (t, J = 6.0 Hz,




2H-pyran-4-
1H), 4.95 (m, 1H), 4.60 (dd, J = 9.4, 6.5 Hz, 1H),




ylcarbonyl)
4.32 (d, J = 6.0 Hz, 3H), 4.26 (m, 1H), 4.11 (dd, J =




azetidin-3-yl]
9.5, 3.8 Hz, 1H), 3.84 (m, 2H), 3.74 (dd, J =




oxy}phenyl)urea
10.6, 3.9 Hz, 1H), 3.36-3.26 (m, 2H), 1.57 (m, 4H)



434
1-(4-{[1-(1,4-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (d,

(ESI(+))



dioxan-2-
2H), 7.88 (s, 1H), 7.51 (s, 1H), 7.37 (s, 1H), 7.33
m/e 452



ylcarbonyl)
(m, 2H), 6.83 (dd, J = 6.9, 1.6 Hz, 1H), 6.74 (m,
(M + H)+



azetidin-3-
2H), 6.64 (t, J=6.0 Hz, 1H), 4.96 (m, 1H), 4.69




yl]oxy}phenyl)-
(m, 1H), 4.30 (m, 3H), 4.18 (m, 2H), 3.76 (m,




3-(imidazo[1,2-
3H), 3.65-3.45 (m, 4H)




a]pyridin-7-





ylmethyl)urea




435
1-(imidazo[1,2-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.51 (s,

(ESI(+))



a]pyridin-7-
1H), 8.48 (dd, J = 6.9, 0.9 Hz, 1H), 7.88 (d, J =
m/e 464



ylmethyl)-3-(4-
1.1 Hz, 1H), 7.51 (d, J = 1.2 Hz, 1H), 7.37 (s,
(M + H)+



{[1-(tetrahydro-
1H), 7.33 (m, 2H), 6.83 (dd, J = 6.9, 1.7 Hz, 1H),




2H-pyran-4-
6.74 (m, 2H), 6.64 (t, J = 6.0 Hz, 1H), 4.94 (m,




ylacetyl)
1H), 4.52 (m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 4.25




azetidin-3-
(m, 1H), 4.04 (dd, J = 9.5, 3.9 Hz, 1H), 3.76 (m,




yl]oxy}phenyl)
3H), 3.27 (m, 2H), 2.02 (d, J = 1.9 Hz, 2H), 1.87




urea
(m, 1H), 1.54 (m, 2H), 1.19 (m, 2H)









Example 436
tert-butyl (3R)-3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 321A-C, substituting (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate for (R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate in Example 321A. 1H NMR (400 MHz, methanol-d4) δ ppm 8.41-8.35 (m, 1H), 7.91-7.83 (m, 2H), 7.81-7.76 (m, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.47-7.43 (m, 1H), 7.06-6.98 (m, 2H), 6.93 (dd, J=7.1, 1.5 Hz, 1H), 5.12-5.05 (m, 1H), 4.62 (bs, 2H), 3.68-3.39 (m, 4H), 2.25-2.13 (m, 2H), 1.49-1.43 (m, 9H); MS (ESI(+)) m/e 437 (M+H)+.


Example 438
1-[4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
Example 438A
1-(2-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)-3,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 438B
1-[4-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(2-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.77-8.70 (m, 1H), 8.19-8.15 (m, 1H), 8.00-7.96 (m, 1H), 7.95-7.88 (m, 1H), 7.80 (s, 1H), 7.53-7.41 (m, 6H), 7.30-7.15 (m, 2H), 6.26-5.95 (m, 1H), 4.61 (bs, 2H), 4.41-4.31 (m, 1H), 4.17-4.08 (m, 1H), 4.02-3.93 (m, 1H), 3.69-3.59 (m, 1H), 2.67-2.52 (m, 2H); MS (ESI(+)) m/e 470 (M+H)+.


Example 439
1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(2-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and 2-(tetrahydro-2H-pyran-4-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.74 (dd, J=7.0, 0.9 Hz, 1H), 8.18-8.15 (m, 1H), 7.98 (d, J=2.2 Hz, 1H), 7.92 (t, J=8.5 Hz, 1H), 7.82-7.78 (m, 1H), 7.47 (dd, J=7.0, 1.6 Hz, 1H), 7.28-7.15 (m, 2H), 6.16-6.10 (m, 1H), 4.61 (bs, 2H), 4.25-4.16 (m, 2H), 3.96-3.87 (m, 2H), 3.83-3.72 (m, 2H), 3.48-3.37 (m, 2H), 2.61-2.54 (m, 1H), 2.53-2.46 (m, 1H), 2.45-2.34 (m, 2H), 2.11-1.97 (m, 1H), 1.73-1.62 (m, 2H), 1.42-1.27 (m, 2H); MS (ESI(+)) m/e 492 (M+H)+.


Example 442
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)urea
Example 442A
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(piperidin-4-yloxy)phenyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 442B
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(piperidin-4-yloxy)phenyl)urea for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.48 (m, 2H), 7.88 (s, 1H), 7.51 (s, 1H), 7.37 (s, 1H), 7.31 (m, 2H), 6.87 (m, 2H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.62 (t, J=6.0 Hz, 1H), 4.48 (m, 1H), 4.32 (d, J=6.0 Hz, 2H), 3.85 (m, 1H), 3.74 (m 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.88 (m, 1H), 1.88 (m, 2H), 1.49 (m, 2H), 0.99 (d, J=6.7 Hz, 6H); (ESI(+)) m/e 436 (M+H)+.


Table 21.


The following Examples were prepared essentially as described in Example 442, substituting the appropriate carboxylic acid in Example 442B.















Ex
Name

1H NMR

MS







443
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



a]pyridin-7-ylmethyl)-
(m, 2H), 7.88 (s, 1H), 7.51 (s, 1H), 7.37 (s,
m/e 450



3-[4-({1-[(2S)-2-
1H), 7.31 (m, 2H), 6.87 (m, 2H), 6.83 (dd, J =
(M + H)+



methylbutanoyl]piperidin-
7.0, 1.6 Hz, 1H), 6.65 (t, J = 6.0 Hz, 1H), 4.49




4-yl}oxy)phenyl]urea
(m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 3.84 (m,





2H), 3.26 (m, 2H), 2.72 (m, 1H), 1.90 (m,





2H), 1.51 (m, 3H), 1.29 (m, 1H), 0.97 (d, J =





6.7 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H)



444
1-(4-{[1-(cyclopropylacetyl)
-1H NMR (500 MHz, DMSO-d6) δ ppm 8.48
(ESI(+))



piperidin-4-yl]oxy}phenyl)-
(m, 2H), 7.88 (s, 1H), 7.51 (s, 1H), 7.37 (s,
m/e 448



3-(imidazo[1,2-
1H), 7.31 (m, 2H), 6.87 (m, 2H), 6.83 (dd, J =
(M + H)+



a]pyridin-7-ylmethyl)urea
7.0, 1.6 Hz, 1H), 6.62 (t, J = 6.0 Hz, 1H), 4.47





(m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 3.85 (m,





1H), 3.66 (m, 1H), 3.30 (m, 1H), 3.22 (m,





1H), 2.26 (d, J = 6.8 Hz, 2H), 1.91 (m, 2H),





1.50 (m, 2H), 0.95 (m, 1H), 0.44 (m, 2H),





0.11 (m, 2H)



445
1-{4-[(1-benzoylpiperidin-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



4-yl)oxy]phenyl}-3-
(m, 2H), 7.88 (s, 1H), 7.51 (s, 1H), 7.44 (m,
m/e 470



(imidazo[1,2-a]pyridin-7-
3H), 7.40 (m, 2H), 7.37 (m, 1H), 7.31 (m,
(M + H)+



ylmethyl)urea
2H), 6.87 (m, 2H), 6.83 (dd, J = 7.0, 1.6 Hz,





1H), 6.63 (t, J = 6.0 Hz, 1H), 4.52 (m, 1H),





4.31 (d, J = 6.0 Hz, 2H), 3.96 (m, 1H), 3.52





m, 1H), 3.45-3.20 (m, 2H), 1.91 (m, 2H),





1.59 (m, 2H)



446
1-(imidazo[1,2-a]pyridin-

1H NMR (400 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



7-ylmethyl)-3-[4-({1-
(m, 2H), 7.88 (m, 1H), 7.51 (d, J = 1.2 Hz,
m/e 466



[(propan-2-
1H), 7.37 (m, 1H), 7.31 (m, 2H), 6.87 (m,
(M + H)+



yloxy)acetyl]piperidin-4-
2H), 6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.64 (m,




yl}oxy)phenyl]urea
1H), 4.49 (m, 1H), 4.32 (d, J = 6.0 Hz, 2H),





4.08 (s, 2H), 3.82 (m, 1H), 3.67 (m, 1H),





3.59 (m, 1H), 3.40-3.15 (m, 2H), 1.90 (m,





2H), 1.52 (m, 2H), 1.10 (d, J = 6.1 Hz, 6H)



447
1-(4-{[1-(2-hydroxy-2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



methylpropanoyl)piperidin-
(m, 2H), 7.88 (s, 1H), 7.52 (d, J = 1.2 Hz,
m/e 452



4-yl]oxy}phenyl)-3-
1H), 7.38 (s, 1H), 7.30 (m, 2H), 6.87 (m, 2H),
(M + H)+



(imidazo[1,2-a]pyridin-7-
6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.62 (t, J = 6.0




ylmethyl)urea
Hz, 1H), 5.39 (s, 1H), 4.48 (m, 1H), 4.32 (d, J =





6.0 Hz, 2H), 4.10-3.40 (m, 2H), 3.40-





3.15 (m, 2H), 1.90 (m, 2H), 1.54 (m, 2H),





1.31 (s, 6H)



448
1-(imidazo[1,2-a]pyridin-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.49

(ESI(+))



7-ylmethyl)-3-[4-({1-
(m, 2H), 7.90 (s, 1H), 7.54 (d, J = 1.2 Hz,
m/e 464



[(2R)-tetrahydrofuran-2-
1H), 7.39 (s, 1H), 7.31 (m, 2H), 6.86 (m, 3H),
(M + H)+



ylcarbonyl]piperidin-
6.62 (t, J = 6.0 Hz, 1H), 4.67 (m, 1H), 4.48




4-yl}oxy)phenyl]urea
(m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 3.78 (m,





4H), 3.45-3.15 (m, 2H), 2.10-1.75 (m, 6H),





1.53 (m, 2H)



449
1-(imidazo[1,2-a]pyridin-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



7-ylmethyl)-3-[4-({1-
(m, 2H), 7.89 (s, 1H), 7.52 (d, J = 1.2 Hz,
m/e 464



[(2S)-tetrahydrofuran-2-
1H), 7.38 (s, 1H), 7.31 (m, 2H), 6.87 (m, 2H),
(M + H)+



ylcarbonyl]piperidin-4-
6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.62 (t, J = 6.0




yl}oxy)phenyl]urea
Hz, 1H), 4.67 (m, 1H), 4.48 (m, 1H), 4.32 (d,





J = 6.0 Hz, 2H), 3.78 (m, 4H), 3.45-3.16 (m,





2H), 2.09-1.92 (m, 2H), 2.09-1.92 (m, 4H),





1.53 (m, 2H)



450
1-(imidazo[1,2-a]pyridin-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



7-ylmethyl)-3-(4-{[1-
(m, 2H), 7.88 (s, 1H), 7.51 (d, J = 1.2 Hz,
m/e 478



(tetrahydro-2H-pyran-4-
1H), 7.38 (s, 1H), 7.31 (m, 2H), 6.87 (m, 2H),
(M + H)+



ylcarbonyl)piperidin-4-
6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.62 (t, J = 6.0




yl]oxy}phenyl)urea
Hz, 1H), 4.48 (m, 1H), 4.32 (d, J = 6.0 Hz,





2H), 3.88-3.71 (m, 4H), 3.38 (m, 2H), 3.34-





3.16 (m, 1H), 3.22 (m, 1H), 2.89 (m, 1H),





1.91 (m, 2H), 1.67-1.40 (m, 6H)



451
1-(imidazo[1,2 -a]pyridin-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.48

(ESI(+))



7-ylmethyl)-3-(4-{[1-
(m, 2H), 7.88 (s, 1H), 7.52 (bs, 1H), 7.38 (bs,
m/e 492



(tetrahydro-2H-pyran-4-
1H), 7.31 (m, 2H), 6.87 (m, 2H), 6.83 (dd, J =
(M + H)+



ylacetyl)piperidin-4-
7.0, 1.5 Hz, 1H), 6.62 (t, J = 6.0 Hz, 1H), 4.47




yl]oxy}phenyl)urea
(m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 3.89-3.75





(m, 3H), 3.70 (m, 1H), 3.40-3.17 (m, 4H),





2.26 (m, 2H), 1.89 (m, 3H), 1.60-1.40 (m,





4H), 1.19 (m, 2H)



726
1-(4-{[1-(3-fluorobenzoyl)

(ESI(+))



piperidin-4-yl]oxy}

m/e 488



phenyl)-3-(imidazo[1,2-

(M + H)+



a]pyridin-7-ylmethyl)urea




727
1-(4-{[1-(2,4-difluoro-

(ESI(+))



benzoyl)piperidin-4-

m/e 506



yl]oxy}phenyl)-3-

(M + H)+



(imidazo[1,2-a]pyridin-





7-ylmethyl)urea




728
1-(4-{[1-(2,5-difluoro-

(ESI(+))



benzoyl)piperidin-4-

m/e 506



yl]oxy}phenyl)-3-

(M + H)+



(imidazo[1,2-a]pyridin-7-





ylmethyl)urea




729
1-(4-{[1-(3,4-difluoro-

(ESI(+))



benzoyl)piperidin-4-

m/e 506



yl]oxy}phenyl)-3-

(M + H)+



(imidazo[1,2-a]pyridin-7-





ylmethyl)urea




730
1-(4-{[1-(3,5-difluoro-

(ESI(+))



benzoyl)piperidin-4-

m/e 506



yl]oxy}phenyl)-3-

(M + H)+



(imidazo[1,2-a]pyridin-7-





ylmethyl)urea









Example 452
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}urea
Example 452A
1-(4-(azetidin-3-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-(4-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)phenyl)azetidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 452B
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}urea

The title compound was prepared as described in Example 1A, substituting 1-(4-(azetidin-3-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s, 1H), 7.39 (m, 3H), 7.22 (m, 2H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.70 (t, J=6.0 Hz, 1H), 4.52 (m, 1H), 4.33 (d, J=6.0 Hz, 2H), 4.20 (m, 1H), 4.08 (dd, J=8.5, 5.3 Hz, 1H), 3.76 (m, 2H), 2.49 (m, 1H), 0.99 (d, J=6.8 Hz, 6H); (ESI(+)) m/e 392 (M+H)+.


Table 22.


The following Examples were prepared essentially as described in Example 452, substituting the appropriate carboxylic acid in Example 452B.















Ex
Name

1H NMR

MS







453
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.48

(ESI(+))



a]pyridin-7-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.52 (s, 1H), 7.40 (m,
m/e 406



ylmethyl)-3-(4-
3H), 7.22 (m, 2H), 6.84 (dd, J = 7.0, 1.6 Hz, 1H), 6.70
(M + H)+



{1-[(2S)-2-
(m, 1H), 4.52 (m, 1H), 4.33 (d, J = 6.0 Hz, 2H), 4.21 (m,




methylbutanoyl]
1H), 4.06 (m, 1H), 3.76 (m, 2H), 2.27 (m, 1H), 1.50 (m,




azetidin-3-
1H), 1.30 (m, 1H), 0.98 (d, J = 6.8 Hz, 3H), 0.84 (t, J =




yl}phenyl)urea
7.4 Hz, 3H)



454
1-{4-[1-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.49

(ESI(+))



(cyclopropyl-
(d, J = 7.0 Hz, 1H), 7.89 (s, 1H), 7.53 (d, J = 1.2 Hz, 1H),
m/e 404



acetyl)azetidin-3-
7.40 (m, 3H), 7.22 (m, 2H), 6.85 (dd, J = 7.0, 1.6 Hz,
(M + H)+



yl]phenyl}-3-
1H), 6.70 (t, J = 6.0 Hz, 1H), 4.45 (m, 1H), 4.33 (d, J =




(imidazo[1,2-
6.0 Hz, 2H), 4.20 (m, 1H), 4.04 (m, 1H), 3.75 (m, 2H),




a]pyridin-7-
2.02 (d, J = 6.8 Hz, 2H), 0.94 (m, 1H), 0.44 (m, 2H), 0.11




ylmethyl)urea
(m, 2H)



455
1-[4-(1-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.68 (s, 1H), 8.48

(ESI(+))



benzoylazetidin-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.68 (m, 2H), 7.52 (m,
m/e 426



3-yl)phenyl]-3-
2H), 7.46 (m, 2H), 7.40 (m, 3H), 7.26 (m, 2H), 6.83 (dd,
(M + H)+



(imidazo[1,2-
J = 7.0, 1.6 Hz, 1H), 6.72 (t, J = 6.0 Hz, 1H), 464 (m,




a]pyridin-7-
1H), 4.44 (m, 1H), 4.33 (d, J = 6.0 Hz, 2H), 4.27 (m,




ylmethyl)urea
1H), 3.98 (m, 1H), 3.85 (m, 1H)



456
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.67 (s, 1H), 8.48

(ESI(+))



a]pyridin-7-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (d, J = 1.2 Hz, 1H),
m/e 422



ylmethyl)-3-(4-
7.40 (m, 3H), 7.22 (m, 2H), 6.83 (dd, J = 7.0, 1.6 Hz,
(M + H)+



{1-[(propan-2-
1H), 6.71 (t, J = 6.0 Hz, 1H), 4.56 (m, 1H), 4.33 (d, J =




yloxy)acetyl]
6.0 Hz, 2H), 4.24 (m, 1H), 4.13 (m, 1H), 3.95 (s, 2H),




azetidin-3-
3.79 (m, 2H), 3.59 (m, 1H), 1.10 (d, J = 6.1 Hz, 6H)




yl}phenyl)urea




457
1-{4-[1-(2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.50

(ESI(+))



hydroxy-2-
(d, J = 7.0 Hz, 1H), 7.90 (s, 1H), 7.54 (d, J = 1.2 Hz, 1H),
m/e 408



methylpropanoyl)
7.40 (m, 3H), 7.21 (m, 2H), 6.86 (dd, J = 7.0, 1.6 Hz,
(M + H)+



azetidin-3-
1H), 6.70 (t, J = 6.0 Hz, 1H), 5.09 (s, 1H), 4.75 (m, 1H),




yl]phenyl}-3-
4.32 (m, 3H), 4.22 (m, 1H), 3.74 (m, 2H), 1.27 (s, 6H)




(imidazo[1,2-





a]pyridin-7-





ylmethyl)urea




458
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.73 (s, 1H), 8.48

(ESI(+))



a]pyridin-7-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s, 1H), 7.40 (m,
m/e 420



ylmethyl)-3-(4-
3H), 7.22 (m, 2H), 6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.78
(M + H)+



{1-[(2R)-
(t, J = 6.0 Hz, 1H), 4.60 (m, 1H), 4.37 (m, 1H), 4.33 (d,




tetrahydrofuran-2-
J = 6.0 Hz, 2H), 4.24 (m, 1H), 4.16 (m, 1H), 3.86-3.69




ylcarbonyl]azeti-
(m, 4H), 2.04 (m, 1H), 1.96 (m, 1H), 1.82 (m, 2H)




din-3-





yl}phenyl)urea




459
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.48

(ESI(+))



a]pyridin-7-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s, 1H), 7.40 (m,
m/e 420



ylmethyl)-3-(4-
3H), 7.22 (m, 2H), 6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.74-
(M + H)+



{1-8 (2S)-
6.67 (m, 1H), 4.60 (m, 1H), 4.37 (m, 1H), 4.33 (d, J =




tetrahydrofuran-2-
6.0 Hz, 2H), 4.23 (m, 1H), 4.15 (m, 1H), 3.85-3.69 (m,




ylcarbonyl]azeti-
4H), 2.04 (m, 1H), 1.96 (m, 1H), 1.81 (m, 2H)




din-3-





yl}phenyl)urea




460
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.67 (s, 1H), 8.48

(ESI(+))



a]pyridin-7-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (d, J = 1.1 Hz, 1H),
m/e 434



ylmethyl)-3-{4-
7.40 (m, 3H), 7.22 (m, 2H), 6.83 (dd, J = 7.0, 1.6 Hz,
(M + H)+



[1-(tetrahydro-
1H), 6.71 (t, J = 6.0 Hz, 1H), 4.54 (m, 1H), 4.33 (d, J =




2H-pyran-4-
6.0 Hz, 2H), 4.21 (m, 1H), 4.13 (m, 1H), 3.85 (m, 2H),




ylcarbonyl)azeti-
3.77 (m, 2H), 3.40-3.25 (m, 2H), 2.50 (m, 1H), 1.58




din-3-
(m, 4H)




yl]phenyl}urea




461
1-(imidazo[1,2-

1H NMR (500 MHz, DMSO-d6) δ ppm 8.70 (s, 1H), 8.48

(ESI(+))



a]pyridin-7-
(d, J = 7.0 Hz, 1H), 7.88 (s, 1H), 7.51 (s, 1H), 7.40 (m,
m/e 448



ylmethyl)-3-{4-
3H), 7.21 (m, 2H), 6.83 (dd, J = 7.0, 1.6 Hz, 1H), 6.75
(M + H)+



[1-(tetrahydro-
(t, J = 6.0 Hz, 1H), 4.47 (m, 1H), 4.33 (d, J = 6.0 Hz,




2H-pyran-4-
2H), 4.19 (m, 1H), 4.05 (m, 1H), 3.85-3.69 (m, 4H), 3.28




ylacetyl)azetidin-
(m, 2H), 2.03 (d, J = 1.8 Hz, 2H), 1.90 (m, 1H), 1.57 (m,




3-yl]phenyl}urea
2H), 1.21 (m, 2H)









Example 462
4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide
Example 462A
methyl 4-(2-cyclopentylacetamido)-2-fluorobenzoate

The title compound was prepared as described in Example 52A, substituting 2-cyclopentylacetyl chloride for 2-cyclopentylacetyl chloride and methyl 4-amino-2-fluorobenzoate for methyl 4-aminobenzoate.


Example 462B
4-(2-cyclopentylacetamido)-2-fluorobenzoic acid

The title compound was prepared as described in Example 4B, substituting methyl 4-(2-cyclopentylacetamido)-2-fluorobenzoate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 462C
4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)-2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (501 MHz, DMSO-d6) δ ppm 10.24 (s, 1H), 8.70-8.63 (m, 1H), 8.46 (s, 1H), 7.95 (s, 1H), 7.74-7.62 (m, 2H), 7.58-7.50 (m, 2H), 7.32 (dd, J=8.5, 1.9 Hz, 1H), 7.24 (dd, J=9.2, 1.7 Hz, 1H), 4.45 (d, J=5.9 Hz, 2H), 2.37-2.31 (m, 2H), 2.31-2.15 (m, 1H), 1.81-1.69 (m, 2H), 1.67-1.45 (m, 4H), 1.25-1.12 (m, 2H); MS (ESI(+)) m/e 395 (M+H)+.


Example 464
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[6-(morpholin-4-yl)pyridin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.34 (t, J=6.0 Hz, 1H), 8.87 (d, J=7.0 Hz, 1H), 8.51 (d, J=2.5 Hz, 1H), 8.33 (d, J=2.2 Hz, 1H), 8.15 (d, J=2.1 Hz, 1H), 7.90 (dd, J=8.9, 2.6 Hz, 1H), 7.85 (d, J=3.9 Hz, 1H), 7.81 (s, 1H), 7.50-7.44 (m, 2H), 6.94 (d, J=9.0 Hz, 1H), 4.67 (d, J=5.9 Hz, 2H), 3.75-3.66 (m, 4H), 3.57-3.49 (m, 4H); MS (ESI(+)) m/e 420 (M+H).


Example 467
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide
Example 467A
tert-butyl 3-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 467B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(pyrrolidin-3-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 467C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(pyrrolidin-3-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.4 Hz, 1H), 8.48 (d, J=6.8 Hz, 1H), 7.88 (s, 1H), 7.68 (dd, J=3.9, 2.2 Hz, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.37 (s, 1H), 7.02 (dd, J=8.1, 3.7 Hz, 1H), 6.82 (dd, J=7.0, 1.5 Hz, 1H), 4.46 (d, J=5.8 Hz, 2H), 3.22-3.94 (m, 5H), 2.21-2.42 (m, 1H), 2.10-2.17 (m, 2H), 1.86-2.09 (m, 2H), 0.86-0.95 (m, 6H); MS (ESI(+)) m/e 411 (M+H)+.


Table 23.


The following Examples were prepared essentially as described in Example 467, using an appropriate carboxylic acid in Example 467C.














Ex
Name
MS







540
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-
(ESI(+))



trifluoropropanoyl)pyrrolidin-3-yl]thiophene-2-
m/e 437



carboxamide
(M + H)+


541
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-
(ESI(+))



methylpropanoyl)pyrrolidin-3-yl]thiophene-2-
m/e 397



carboxamide
(M + H)+


542
5-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)thiophene-2-carboxamide
m/e 431




(M + H)+


717
5-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 395



carboxamide
(M + H)+


718
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-
(ESI(+))



methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 445




(M + H)+


756
5-[1-(cyclopropylacetyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 409




(M + H)+


757
5-[1-(2-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 465




(M + H)+


758
5-{1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 463



carboxamide
(M + H)+


759
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-
(ESI(+))



methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 461




(M + H)+


760
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-
(ESI(+))



methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 461




(M + H)+


761
5-{1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 463



carboxamide
(M + H)+


762
5-[1-(3-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 449




(M + H)+


763
5-[1-(4-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 449




(M + H)+


764
5-{1[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 481



carboxamide
(M + H)+


765
5-{1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 463



carboxamide
(M + H)+


766
5-[1-(4-cyanobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 456




(M + H)+


767
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyl-
(ESI(+))



oxetan-3-yl) carbonyl]pyrrolidin-3-yl}thiophene-2-
m/e 425



carboxamide
(M + H)+


768
5-[1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 467



carboxamide
(M + H)+


769
5-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 421



carboxamide
(M + H)+


770
5-[1-(4-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 465




(M + H)+


771
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-
(ESI(+))



1H-pyrrol-2-yl) carbonyl]pyrrolidin-3-yl}thiophene-2-
m/e 434



carboxamide
(M + H)+


772
5-[1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 467



carboxamide
(M + H)+


773
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-4-
(ESI(+))



ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 432




(M + H)+


774
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-2-
(ESI(+))



ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 432




(M + H)+


775
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-
(ESI(+))



1H-pyrazol-4 -yl)carbonyl]pyrrolidin-3-yl}thiophene-2-
m/e 435



carboxamide
(M + H)+


776
5-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 449




(M + H)+


777
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2E)-2-
(ESI(+))



methylpent-2-enoyl]pyrrolidin-3-yl}thiophene-2-
m/e 423



carboxamide
(M + H)+


778
5-{1-[(2,5-dimethylfuran-3-yl)carbonyl]pyrrolidin-3-yl}-
(ESI(+))



N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 449



carboxamide
(M + H)+


779
5-[1-(3-chlorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 465




(M + H)+


780
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-propanoyl-
(ESI(+))



pyrrolidin-3-yl)thiophene-2-carboxamide
m/e 383




(M + H)+


781
5-{1-[(1-cyanocyclopropyl)carbonyl]pyrrolidin-3-yl}-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 420



carboxamide
(M + H)+


782
5-(1-butanoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-
(ESI(+))



ylmethyl)thiophene-2-carboxamide
m/e 397




(M + H)+


783
5-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-
(ESI(+))



a]pyridin-7-ylmethyl)thiophene-2-carboxamide
m/e 421




(M + H)+


784
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4-
(ESI(+))



methoxybenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 461




(M + H)+


785
5-[1-(2,5-difluorobenzoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 467



carboxamide
(M + H)+


786
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(thiophen-2-
(ESI(+))



ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 437




(M + H)+


787
5-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 411



carboxamide
(M + H)+


788
5-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 425



carboxamide
(M + H)+


791
5-[1-(2,2 -dimethylbutanoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 425



carboxamide
(M + H)+


792
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyrazin-2-
(ESI(+))



ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 433




(M + H)+


793
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methyl-
(ESI(+))



thiophen-2-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-
m/e 451



carboxamide
(M + H)+


794
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-
(ESI(+))



methylbenzoyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 445




(M + H)+


795
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-
(ESI(+))



methylcyclopropyl)carbonyl]pyrrolidin-3-yl}thiophene-2-
m/e 409



carboxamide
(M + H)+


796
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-
(ESI(+))



trifluorobutanoyl)pyrrolidin-3-yl]thiophene-2-
m/e 451



carboxamide
(M + H)+


797
5-{1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]pyrrolidin-
(ESI(+))



3-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 450



carboxamide
(M + H)+


798
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(pyridin-3-
(ESI(+))



ylcarbonyl)pyrrolidin-3-yl]thiophene-2-carboxamide
m/e 432




(M + H)+


799
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(1-methyl-
(ESI(+))



1H-pyrazol-5-yl)carbonyl]pyrrolidin-3-yl}thiophene-2-
m/e 435



carboxamide
(M + H)+


800
5-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-
m/e 425



carboxamide
(M + H)+









Example 468
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropanoyl)amino]cyclobutyl}thiophene-2-carboxamide
Example 468A
5-(1-(1,1-dimethylethylsulfinamido)cyclobutyl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 324A, substituting N-cyclobutylidene-2-methylpropane-2-sulfinamide for N-(oxetan-3-ylidene)propane-2-sulfinamide.


Example 468B
5-(1-(1,1-dimethylethylsulfinamido)cyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(1-(1,1-dimethylethylsulfinamido)cyclobutyl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 468C
5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared in Example 324C, substituting 5-(1-(1,1-dimethylethylsulfinamido)cyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 5-(3-(1,1-dimethylethylsulfinamido)oxetan-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide.


Example 468D

The title compound was prepared as described in Example 1A, substituting 5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.97 (t, J=5.9 Hz, 1H), 8.53 (s, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.63 (d, J=3.7 Hz, 1H), 7.52 (d, J=1.4 Hz, 1H), 7.38 (s, 1H), 7.04 (d, J=3.7 Hz, 1H), 6.82 (dd, J=6.8, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 2.36-2.48 (m, 5H), 1.86-2.01 (m, 2H), 0.99 (d, J=6.8 Hz, 6H); MS (ESI(+)) m/e 397 (M+H)+.


Example 469
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3-methylbutanoyl)amino]cyclobutyl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.97 (t, J=5.9 Hz, 1H), 8.59 (s, 1H), 8.48 (d, J=7.8 Hz, 1H), 7.88 (s, 1H), 7.63 (d, J=4.1 Hz, 1H), 7.51 (d, J=1.0 Hz, 1H), 7.37 (s, 1H), 7.05 (d, J=3.7 Hz, 1H), 6.82 (dd, J=7.1, 1.7 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 2.39-2.47 (m, 4H), 1.83-2.03 (m, 5H), 0.87 (d, J=6.4 Hz, 6H); MS (ESI(+)) m/e 411 (M+H)+.


Example 470
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1-{[(2S)-2-methylbutanoyl]amino}cyclobutyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 8.97 (t, J=6.1 Hz, 1H), 8.57 (s, 1H), 8.47 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.63 (d, J=4.1 Hz, 1H), 7.51 (d, J=1.4 Hz, 1H), 7.37 (s, 1H), 7.04 (d, J=3.7 Hz, 1H), 6.82 (dd, J=7.0, 1.5 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 2.37-2.49 (m, 4H), 2.13-2.26 (m, 1H), 1.84-2.01 (m, 2H), 1.40-1.59 (m, 1H), 1.20-1.36 (m, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.82 (t, J=7.3 Hz, 3H); MS (ESI(+)) m/e 411 (M+H)+.


Example 471
5-[1-(benzoylamino)cyclobutyl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.17 (s, 1H), 8.98 (t, J=5.9 Hz, 1H), 8.46 (d, J=6.1 Hz, 1H), 7.84-7.90 (m, 3H), 7.65 (d, J=4.1 Hz, 1H), 7.43-7.57 (m, 4H), 7.37 (s, 1H), 7.14 (d, J=4.1 Hz, 1H), 6.81 (dd, J=6.8, 1.7 Hz, 1H), 4.44 (d, J=6.1 Hz, 2H), 2.61-2.73 (m, 2H), 2.50-2.60 (m, 2H), 1.91-2.07 (m, 2H); MS (ESI(+)) m/e 431 (M+H)+.


Example 472
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3,3,3-trifluoropropanoyl)amino]cyclobutyl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3,3,3-trifluoropropanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.08 (s, 1H), 9.00 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.8 Hz, 1H), 7.88 (s, 1H), 7.65 (d, J=3.7 Hz, 1H), 7.52 (s, 1H), 7.38 (s, 1H), 7.07 (d, J=3.7 Hz, 1H), 6.83 (dd, J=6.8, 1.7 Hz, 1H), 4.46 (d, J=5.8 Hz, 2H), 3.19-3.36 (m, 2H), 2.43-2.53 (m, 4H), 1.86-2.03 (m, 2H); MS (ESI(+)) m/e 437 (M+H)+.


Example 473
N-(1-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}cyclobutyl)tetrahydro-2H-pyran-4-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(1-aminocyclobutyl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and tetrahydro-2H-pyran-4-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.97 (t, J=6.1 Hz, 1H), 8.60 (s, 1H), 8.48 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.63 (d, J=3.7 Hz, 1H), 7.51 (d, J=1.0 Hz, 1H), 7.37 (s, 1H), 7.04 (d, J=3.7 Hz, 1H), 6.82 (dd, J=7.0, 1.5 Hz, 1H), 4.45 (d, J=5.8 Hz, 2H), 3.81-3.89 (m, 2H), 3.24-3.36 (m, 2H), 2.33-2.48 (m, 5H), 1.84-2.00 (m, 2H), 1.47-1.65 (m, 4H); MS (ESI(+)) m/e 439 (M+H)+.


Example 474
tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxyl}azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)azetidin-3-yloxy)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.98 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.89 (m, 3H), 7.51 (d, J=1.1 Hz, 1H), 7.37 (s, 1H), 6.92 (m, 2H), 6.84 (dd, J=7.0, 1.6 Hz, 1H), 5.06 (m, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.33 (m, 2H), 3.80 (m, 2H), 1.39 (s, 9H); MS (ESI(+)) m/e 423 (M+H)+.


Example 485
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide
Example 485A
tert-butyl 4-((4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)thiophen-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline.


Example 485B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-((4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)thiophen-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate. 1H NMR (300 MHz, methanol-d4) δ 8.76 (dd, J=7.1, 0.9 Hz, 1H), 8.19 (dd, J=2.2, 0.7 Hz, 1H), 8.07 (s, 1H), 8.00 (d, J=2.2 Hz, 1H), 7.83 (d, J=0.6 Hz, 2H), 7.72 (d, J=3.8 Hz, 1H), 7.49 (dd, J=7.0, 1.6 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 4.75 (s, 2H), 4.15 (d, J=7.0 Hz, 2H), 3.48-3.36 (m, 2H), 3.08-2.91 (m, 2H), 2.37-2.15 (m, 1H), 1.85 (d, J=14.0 Hz, 2H), 1.63-1.43 (m, 2H); MS (ESI(+)) m/e 421 (M+H)+.


Example 486
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea
Example 486A
1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

To a solution of imidazo[1,2-a]pyridin-7-ylmethanamine (500 mg, 3.40 mmol) in dichloromethane (17 ml) at room temperature was added 1-bromo-4-isocyanatobenzene (680 mg, 3.40 mmol) as a single portion. The resulting suspension was stirred overnight and then filtered with dichloromethane washes to give the title compound.


Example 486B
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}urea

The title compound was prepared as described in Example 51A, substituting substituting 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.62 (s, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 8.02 (d, J=0.8 Hz, 1H), 7.88 (dd, J=1.2, 0.7 Hz, 1H), 7.77 (d, J=0.8 Hz, 1H), 7.54-7.34 (m, 6H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.69 (t, J=6.0 Hz, 1H), 4.34 (d, J=5.9 Hz, 2H), 3.90 (d, J=7.1 Hz, 2H), 2.21-2.04 (m, 1H), 0.86 (d, J=6.7 Hz, 6H). MS (ESI(+)) m/e 389 (M+H)+.


Example 487
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]urea

The title compound was prepared as described in Example 51A, substituting 1-propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 8.04 (d, J=0.8 Hz, 1H), 7.90-7.86 (m, 1H), 7.76 (d, J=0.8 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.46-7.35 (m, 5H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.69 (t, J=6.0 Hz, 1H), 4.34 (d, J=5.9 Hz, 2H), 4.04 (t, J=6.9 Hz, 2H), 1.91-1.73 (m, 2H), 1.26-1.05 (m, 1H), 0.85 (t, J=7.4 Hz, 3H); MS (ESI(+)) m/e 375 (M+H)+.


Example 489
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-phenoxybenzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-phenoxybenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.95 (m, 2H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.44 (m, 2H), 7.38 (s, 1H), 7.22 (m, 1H), 7.14-6.98 (m, 4H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.50 (d, J=5.9 Hz, 2H); MS (ESI(+)) m/e 344 (M+H)+.


Example 490
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)azetidin-3-yl]benzamide
Example 490A
4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 490B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpropanoyl)azetidin-3-yl]benzamide

The title compound was prepared as described in Example 1A, substituting -(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 3-methylbutan-1-amine and 2-methylpropanoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.10 (t, J=5.9 Hz, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.91 (m, 3H), 7.52 (d, J=1.0 Hz, 1H), 7.48 (m, 2H), 7.38 (s, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.58 (t, J=8.6 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.26 (t, J=9.0 Hz, 1H), 4.18 (dd, J=8.4, 6.0 Hz, 1H), 3.92 (m, 1H), 3.84 (m, 1H), 3.17 (d, J=5.0 Hz, 1H), 1.00 (dd, J=6.8, 1.6 Hz, 6H); MS (ESI(+)) m/e 377 (M+H)+.


Table 24.


The following Examples were prepared essentially as described in Example 490, using an appropriate carboxylic acid in Example 490B.














Ex
Name
MS







547
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2S)-2-
(ESI(+))



methylbutanoyl]azetidin-3-yl}benzamide
m/e 391




(M + H)+


548
4-[1-(cyclopropylacetyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 389




(M + H)+


549
4-(1-benzoylazetidin-3-yl)-N-(imidazo[1,2 -a]pyridin-
(ESI(+))



7-ylmethyl)benzamide
m/e 411




(M + H)+


550
4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]-
(ESI(+))



N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 393




(M + H)+


551
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(tetrahydro-
(ESI(+))



2H-pyran-4-ylacetyl)azetidin-3-yl]benzamide
m/e 433




(M + H)+


552
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-
(ESI(+))



2-ylcarbonyl)azetidin-3-yl]benzamide
m/e 417




(M + H)+


628
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(2-
(ESI(+))



methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide
m/e 389




(M + H)+


629
4-[1-(cyclopentylacetyl)azetidin-3 -yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 417




(M + H)+


630
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
(ESI(+))



methylpentanoyl)azetidin-3-yl]benzamide
m/e 405




(M + H)+


631
4-[1-(cyclopentylcarbonyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 403




(M + H)+


632
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-
(ESI(+))



methylcyclopropyl)carbonyl]azetidin-3-yl}benzamide
m/e 389




(M + H)+


633
4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 391




(M + H)+


634
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-
(ESI(+))



thiazol-5-ylcarbonyl)azetidin-3-yl]benzamide
m/e 418




(M + H)+


635
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrazin-
(ESI(+))



2-ylcarbonyl)azetidin-3-yl]benzamide
m/e 413




(M + H)+


636
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
(ESI(+))



methoxybenzoyl)azetidin-3-yl]benzamide
m/e 441




(M + H)+


637
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(1,3-
(ESI(+))



thiazol-4-ylcarbonyl)azetidin-3-yl]benzamide
m/e 418




(M + H)+


638
4-[1-(2-fluorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 429




(M + H)+


639
4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 401




(M + H)+


640
4-[1-(3-fluorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 429




(M + H)+


641
4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 447




(M + H)+


642
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-
(ESI(+))



methyl-1H-pyrazol-3-yl)carbonyl]azetidin-3-
m/e 415



yl}benzamide
(M + H)+


643
4-[1-(2-chlorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 445




(M + H)+


644
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-
(ESI(+))



methylbenzoyl)azetidin-3-yl]benzamide
m/e 425




(M + H)+


645
4-[1-(4-chlorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 445




(M + H)+


646
4-[1-(3-chlorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 445




(M + H)+


647
4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 405




(M + H)+


648
4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 447




(M + H)+


649
4-[1-(4-fluorobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 429




(M + H)+


650
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-
(ESI(+))



methylbenzoyl)azetidin-3-yl]benzamide
m/e 425




(M + H)+


651
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
(ESI(+))



methylbutanoyl)azetidin-3-yl]benzamide
m/e 391




(M + H)+


652
4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]-
(ESI(+))



N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 405




(M + H)+


653
4-[1-(3-cyanobenzoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 436




(M + H)+


654
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
(ESI(+))



methoxybenzoyl)azetidin-3-yl]benzamide
m/e 441




(M + H)+


655
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(4-
(ESI(+))



methoxybenzoyl)azetidin-3-yl]benzamide
m/e 441




(M + H)+


565
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-
(ESI(+))



[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-
m/e 414



yl}benzamide
(M + H)+


657
4-[1-(cyclohexylacetyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 431




(M + H)+


658
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-
(ESI(+))



(pyridin-4-ylcarbonyl)azetidin-3-yl]benzamide
m/e 412




(M + H)+


659
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-
(ESI(+))



(pyridin-3-ylcarbonyl)azetidin-3-yl]benzamide
m/e 412




(M + H)+


660
4-[1-(cyclohexylcarbonyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 417




(M + H)+


661
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-
(ESI(+))



(pyridin-2-ylcarbonyl)azetidin-3-yl]benzamide
m/e 412




(M + H)+


662
4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 401




(M + H)+


663
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-
(ESI(+))



(pyrimidin-4-ylcarbonyl)azetidin-3-yl]benzamide
m/e 413




(M + H)+


664
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-
(ESI(+))



(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]benzamide
m/e 418




(M + H)+


665
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[(1-
(ESI(+))



methylcyclohexyl)carbonyl]azetidin-3-yl}benzamide
m/e 431




(M + H)+


666
4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]-N-
(ESI(+))



(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide
m/e 405




(M + H)+


667
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(3-
(ESI(+))



methylbenzoyl)azetidin-3-yl]benzamide
m/e 425




(M + H)+


668
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(thiophen-
(ESI(+))



3-ylcarbonyl)azetidin-3-yl]benzamide
m/e 417




(M + H)+


669
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-
(ESI(+))



(trifluoromethoxy)benzoyl]azetidin-3-yl}benzamide
m/e 495




(M + H)+


670
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-
(ESI(+))



[(3-methylthiophen-2-yl)carbonyl]azetidin-3-
m/e 431



yl}benzamide
(M + H)+


671
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[3-
(ESI(+))



(trifluoromethyl)benzoyl]azetidin-3-yl}benzamide
m/e 479




(M + H)+









Example 491
tert-butyl 4-{4-[(3-chloroimidazo[1,2-a]pyridin-6-yl)carbamoyl]phenyl}piperidine-1-carboxylate

A solution of tert-butyl 4-(4-(imidazo[1,2-a]pyridin-6-ylcarbamoyl)phenyl)piperidine-1-carboxylate (0.015 g, 0.036 mmol) in chloroform (0.618 ml) and methanol (0.095 ml) was treated with N-chlorosuccinimide (5.24 mg, 0.039 mmol) and the reaction was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated under a stream of warm nitrogen. The residue was purified by normal phase flash chromatography to provide the title compound. 1H NMR (500 MHz, methanol-d4) δ ppm 9.23 (s, 1H), 7.93 (d, J=8.3 Hz, 2H), 7.62-7.51 (m, 3H), 7.42 (d, J=8.3 Hz, 2H), 4.27-4.19 (m, 2H), 2.96-2.76 (m, 3H), 1.90-1.82 (m, 2H), 1.70-1.57 (m, 2H), 1.48 (s, 9H); MS (ESI(+)) m/e 455 (M+H)+.


Example 492
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide
Example 492A
(R)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl (3R)-3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 492B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}benzamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 8.75 (d, J=7.0 Hz, 1H), 8.17 (d, J=2.2 Hz, 1H), 7.99 (d, J=2.2 Hz, 1H), 7.94-7.86 (m, 2H), 7.80 (bs, 1H), 7.48 (dd, J=7.0, 1.6 Hz, 1H), 7.11-7.01 (m, 2H), 5.23-5.11 (m, 1H), 4.76 (s, 2H), 3.92-3.47 (m, 4H), 2.87-2.64 (m, 1H), 2.36-2.16 (m, 2H), 1.16-1.01 (m, 6H); MS (ESI(+)) m/e 407 (M+H)+.


Example 493
4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 8.74 (t, J=6.6 Hz, 1H), 8.20-8.14 (m, 1H), 8.01-7.96 (m, 1H), 7.92 (d, J=8.7 Hz, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.82-7.76 (m, 1H), 7.59-7.39 (m, 6H), 7.10 (d, J=8.6 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 5.24-5.07 (m, 1H), 4.75 (d, J=12.3 Hz, 2H), 3.99-3.70 (m, 3H), 3.66-3.56 (m, 1H), 2.39-2.19 (m, 2H); MS (ESI(+)) m/e 441 (M+H)+.


Example 494
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]pyrrolidin-3-yl}oxy)benzamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide for 3-methylbutan-1-amine and (S)-tetrahydrofuran-3-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 8.75 (d, J=7.0 Hz, 1H), 8.19-8.15 (m, 1H), 8.01-7.97 (m, 1H), 7.93-7.86 (m, 2H), 7.82-7.77 (m, 1H), 7.51-7.45 (m, 1H), 7.10-7.01 (m, 2H), 5.23-5.12 (m, 1H), 4.75 (s, 2H), 4.05-3.92 (m, 1H), 3.94-3.63 (m, 7H), 3.57-3.34 (m, 1H), 2.40-2.29 (m, 1H), 2.27-1.97 (m, 3H); MS (ESI(+)) m/e 435 (M+H)+.


Example 495
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({(3R)-1-[(25)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)benzamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yloxy)benzamide for 3-methylbutan-1-amine and (S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 8.75 (d, J=7.0 Hz, 1H), 8.17 (d, J=2.2 Hz, 1H), 7.99 (d, J=2.2 Hz, 1H), 7.94-7.86 (m, 2H), 7.82-7.77 (m, 1H), 7.48 (d, J=7.1 Hz, 1H), 7.10-7.00 (m, 2H), 5.22-5.11 (m, 1H), 4.76 (s, 2H), 3.91-3.49 (m, 4H), 2.70-2.49 (m, 1H), 2.35-2.17 (m, 2H), 1.73-1.59 (m, 1H), 1.50-1.36 (m, 1H), 1.14-1.03 (m, 3H), 0.93-0.86 (m, 3H); MS (ESI(+)) m/e 421 (M+H)+.


Example 496
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-phenoxyphenyl)urea

The title compound was prepared as described in Example 1C, substituting 4-phenoxyaniline for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.68 (s, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (t, J=0.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.44 (m, 2H), 7.39 (m, 1H), 7.34 (m, 2H), 7.07 (m, 1H), 6.93 (m, 4H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.70 (t, J=6.0 Hz, 1H), 4.34 (d, J=6.0 Hz, 2H); MS (ESI(+)) m/e 359 (M+H)+.


Example 497
5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 497A
5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 51A, substituting 5-bromothiophene-2-carboxylic acid for 4-bromoaniline.


Example 497B
5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.11 (t, J=6.0 Hz, 1H), 8.90 (dd, J=7.1, 1.0 Hz, 1H), 8.46 (s, 1H), 8.15 (d, J=0.9 Hz, 1H), 7.81 (s, 1H), 7.75 (d, J=3.9 Hz, 1H), 7.71-7.64 (m, 1H), 7.23 (d, J=3.8 Hz, 1H), 7.16 (dd, J=7.1, 1.8 Hz, 1H), 4.58 (d, J=5.8 Hz, 2H), 3.93 (d, J=7.1 Hz, 2H), 2.20-2.04 (m, 1H), 0.86 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 381 (M+H)+.


Example 543
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide
Example 543A
2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 2-bromothiazole-5-carboxylic acid for 4-nitrobenzoic acid.


Example 543B
tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)thiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 2-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiazole-5-carboxamide for 4-bromoaniline.


Example 543C
tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)thiazol-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)thiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 543D
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(piperidin-4-yl)thiazole-5-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)thiazol-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 543E
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(piperidin-4-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.23 (t, J=6.0 Hz, 1H), 8.49 (d, J=7.0 Hz, 1H), 8.33 (s, 1H), 7.89 (bs, 1H), 7.52 (d, J=1.0 Hz, 1H), 7.40 (bs, 1H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 4.48 (d, J=6.1 Hz, 2H), 4.44 (d, J=13.4 Hz, 1H), 4.02 (d, J=13.1 Hz, 1H), 3.34-3.27 (m, 1H), 3.19 (t, J=11.9 Hz, 1H), 2.95-2.84 (m, 1H), 2.72 (t, J=12.1 Hz, 1H), 2.13-2.02 (m, 2H), 1.68-1.43 (m, 2H), 1.04-0.96 (m, 6H); MS (ESI(+)) m/e 412 (M+H)+.


Example 544
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)piperidin-4-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(piperidin-4-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ππμ 9.23 (t, J=5.9 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.33 (s, 1H), 7.92-7.87 (m, 1H), 7.53 (d, J=1.2 Hz, 1H), 7.40 (d, J=1.6 Hz, 1H), 6.84 (dd, J=6.9, 1.7 Hz, 1H), 4.51-4.41 (m, 3H), 3.96 (d, J=13.8 Hz, 1H), 3.34-3.24 (m, 1H), 3.16 (t, J=11.7 Hz, 1H), 2.71 (t, J=12.2 Hz, 1H), 2.21 (dd, J=7.0, 2.3 Hz, 2H), 2.10-2.00 (m, 2H), 1.61 (qd, J=12.7, 4.3 Hz, 1H), 1.49 (qd, J=12.5, 4.4 Hz, 1H), 0.90 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 426 (M+H)+.


Example 545
2-(1-benzoylpiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(piperidin-4-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.24 (t, J=5.9 Hz, 1H), 8.49 (d, J=7.0 Hz, 1H), 8.34 (s, 1H), 7.89 (s, 1H), 7.53 (d, J=1.1 Hz, 1H), 7.43 (ddd, J=9.6, 6.8, 3.7 Hz, 6H), 6.84 (dd, J=7.0, 1.6 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.48 (d, J=5.9 Hz, 1H), 3.72-3.58 (m, 1H), 3.26-3.13 (m, 1H), 3.06-2.91 (m, 1H), 2.17-1.95 (m, 2H), 1.72-1.62 (m, 2H); MS (ESI(+)) m/e 446 (M+H)+.


Example 546
4-[(cyclopentylacetyl)amino]-N-([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 8.78-8.72 (m, 1H), 8.40 (s, 1H), 7.90-7.83 (m, 2H), 7.75-7.67 (m, 3H), 7.25 (dd, J=7.0, 1.8 Hz, 1H), 4.75-4.69 (m, 2H), 2.44-2.25 (m, 3H), 1.95-1.76 (m, 2H), 1.78-1.50 (m, 4H), 1.35-1.17 (m, 2H); MS (ESI(+)) m/e 378 (M+H)+.


Example 553
5-[4-hydroxy-1-(3-methylbutanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 553A
5-(4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-hydroxy-4-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophen-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 553B
5-[3-hydroxy-1-(2-methylpropanoyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 2-methylpropanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.98 (t, J=6.0 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90-7.87 (m, 1H), 7.65 (d, J=3.8 Hz, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 7.00 (d, J=3.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 5.76 (s, 1H), 4.46 (d, J=5.9 Hz, 2H), 4.33-4.23 (m, 1H), 3.81-3.71 (m, 1H), 2.99-2.85 (m, 1H), 2.21 (d, J=7.0 Hz, 2H), 2.07-1.91 (m, 1H), 1.86-1.71 (m, 4H), 0.94-0.87 (m, 6H); MS (ESI(+)) m/e 441 (M+H)+.


Example 554
5-[4-hydroxy-1-(2-methylpropanoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.98 (s, 1H), 8.48 (d, J=7.0 Hz, 1H), 7.88 (s, 1H), 7.65 (d, J=3.8 Hz, 1H), 7.51 (d, J=1.1 Hz, 1H), 7.37 (s, 1H), 7.01 (d, J=3.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 5.77 (s, 1H), 4.46 (d, J=5.6 Hz, 2H), 4.33-4.22 (m, 1H), 3.88-3.74 (m, 1H), 2.98-2.82 (m, 2H), 1.82 (s, 4H), 1.05-0.96 (m, 6H); MS (ESI(+)) m/e 427 (M+H)+.


Example 555
5-[1-(3,3-dimethylbutanoyl)-4-hydroxypiperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3,3-dimethylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.98 (t, J=5.8 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.91-7.86 (m, 1H), 7.65 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 7.00 (d, J=3.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 5.76 (s, 1H), 4.46 (d, J=6.0 Hz, 2H), 4.38-4.28 (m, 1H), 3.89-3.78 (m, 1H), 2.97-2.85 (m, 1H), 2.38-2.13 (m, 3H), 1.86-1.71 (m, 4H), 0.99 (s, 9H); MS (ESI(+)) m/e 455 (M+H)+.


Example 556
5-(1-benzoyl-4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(4-hydroxypiperidin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.98 (s, 1H), 8.48 (d, J=6.2 Hz, 1H), 7.88 (s, 1H), 7.66 (d, J=3.8 Hz, 1H), 7.53-7.35 (m, 7H), 7.06 (d, J=3.8 Hz, 1H), 6.83 (d, J=7.0 Hz, 1H), 5.83 (s, 1H), 4.46 (d, J=5.9 Hz, 3H), 4.52-4.26 (m, 1H), 1.93 (s, 5H); MS (ESI(+)) m/e 461 (M+H)+.


Example 557
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)azetidin-3-yl]benzamide
Example 557A
tert-butyl 3-(4-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)phenyl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)azetidin-3-yl)benzoic acid for 4-nitrobenzoic acid.


Example 557B
4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-(4-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)phenyl)azetidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 557C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)azetidin-3-yl]benzamide

In a 4 mL vial was mixed 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide bis(2,2,2-trifluoroacetate) (60 mg, 0.112 mmol) in anhydrous tetrahydrofuran (2 mL) at room temperature. To this mixture was added in portions 60% sodium hydride in mineral oil (22.45 mg, 0.561 mmol). This heterogeneous mixture was stirred 1 hour. To this was added propane-2-sulfonyl chloride (0.015 mL, 0.135 mmol) at and reaction mixture was stirred for 3 hours. The mixture was quenched with water, and product was extracted with 10% methanol/dichloromethane. The organic layers were combined, concentrated and purified by normal phase chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (m, 1H), 8.47 (d, J=7.0 Hz, 1H), 7.90 (m, 3H), 7.48 (m, 3H), 7.37 (s, 1H), 6.84 (m, 1H), 4.50 (d, J=5.9 Hz, 2H), 4.22 (m, 2H), 3.93 (m, 3H), 3.48 (m, 1H), 1.25 (d, J=5.9 Hz, 6H); MS (ESI(+)) m/e 413 (M+H)+.


Example 558
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}benzamide
Example 558A
4-(azetidin-3-yloxy)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenoxy}azetidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 558B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}benzamide

The title compound was prepared as described in Example 1A, substituting 4-(azetidin-3-yloxy)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.99 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (m, 1H), 6.95 (m, 2H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 5.11 (m, 1H), 4.64 (dd, J=9.5, 6.4 Hz, 1H), 4.49 (d, J=5.8 Hz, 2H), 4.32 (dd, J=10.4, 6.3 Hz, 1H), 4.09 (m, 1H), 3.78 (dd, J=10.6, 3.9 Hz, 1H), 2.48 (m, 1H), 0.98 (t, J=6.7 Hz, 6H); MS (ESI(+)) m/e 393 (M+H)+.


Example 559
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)benzamide

The title compound was prepared as described in Example 1A, substituting 4-(azetidin-3-yloxy)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 3-methylbutan-1-amine and (2S)-2-methylbutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.99 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 6.95 (m, 2H), 6.85 (dd, J=6.9, 1.6 Hz, 1H), 5.11 (dd, J=6.4, 3.5 Hz, 1H), 4.63 (dd, J=9.5, 6.5 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.33 (m, 1H), 4.11 (m, 1H), 3.79 (m, 1H), 2.29 (m, 1H), 1.50 (m, 1H), 1.28 (m, 1H), 0.97 (t, J=6.0 Hz, 3H), 0.82 (m, 3H); MS (ESI(+)) m/e 407 (M+H)+.


Example 560
4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting 4-(azetidin-3-yloxy)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 3-methylbutan-1-amine and cyclopropylacetic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.99 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 6.94 (m, 2H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 5.10 (m, 1H), 4.57 (dd, J=9.5, 6.5 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.33 (dd, J=10.6, 6.5 Hz, 1H), 4.08 (dd, J=9.6, 3.8 Hz, 1H), 3.78 (dd, J=10.6, 3.9 Hz, 1H), 2.03 (d, J=6.8 Hz, 2H), 0.91 (m, 1H), 0.44 (m, 2H), 0.10 (m, 2H); MS (ESI(+)) m/e 405 (M+H)+.


Example 561
4-[(1-benzoylazetidin-3-yl)oxy]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting 4-(azetidin-3-yloxy)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.99 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.90 (m, 3H), 7.66 (m, 2H), 7.59-7.42 (m, 4H), 7.37 (s, 1H), 6.95 (m, 2H), 6.84 (dd, J=6.9, 1.7 Hz, 1H), 5.17 (m, 1H), 4.71 (m, 1H), 4.57 (m, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.33 (m, 1H), 4.02 (m, 1H); MS (ESI(+)) m/e 427 (M+H)+.


Example 563
tert-butyl 4-{4-[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.11 (t, J=5.9 Hz, 1H), 8.89 (dd, J=7.0, 0.9 Hz, 1H), 8.44 (s, 1H), 7.89-7.83 (m, 2H), 7.67-7.65 (m, 1H), 7.40-7.34 (m, 2H), 7.15 (dd, J=7.0, 1.8 Hz, 1H), 4.62-4.57 (m, 2H), 4.14-4.03 (m, 2H), 2.91-2.67 (m, 3H), 1.82-1.71 (m, 2H), 1.60-1.37 (m, 11H); MS (ESI(+)) m/e 436 (M+H)+.


Example 564
2-cyclopentyl-N-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)acetamide

The title compound was prepared as described in Example 1C, substituting N-(4-aminophenyl)-2-cyclopentylacetamide for 4-amino-N-isopentylbenzamide and [1,2,4]triazolo[1,5-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.68 (s, 1H), 8.89 (d, J=7.0 Hz, 1H), 8.64 (s, 1H), 8.45 (s, 1H), 7.65 (s, 1H), 7.47-7.41 (m, 2H), 7.34-7.28 (m, 2H), 7.14 (dd, J=7.0, 1.8 Hz, 1H), 6.78 (t, J=6.0 Hz, 1H), 4.42 (d, J=6.0 Hz, 2H), 2.29-2.15 (m, 3H), 1.79-1.68 (m, 2H), 1.66-1.43 (m, 4H), 1.24-1.11 (m, 2H); MS (ESI(+)) m/e 393 (M+H)+.


Example 565
tert-butyl 4-(4-{[([1,2,4]triazolo[1,5-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide and [1,2,4]triazolo[1,5-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.89 (d, J=7.0 Hz, 1H), 8.66 (s, 1H), 8.45 (s, 1H), 7.64 (s, 1H), 7.36-7.30 (m, 2H), 7.14 (dd, J=7.0, 1.8 Hz, 1H), 7.12-7.07 (m, 2H), 6.80 (t, J=6.0 Hz, 1H), 4.43 (d, J=6.0 Hz, 2H), 4.10-4.00 (m, 2H), 2.90-2.63 (m, 2H), 2.66-2.54 (m, 1H), 1.75-1.67 (m, 2H), 1.49-1.35 (s, 11H); MS (ESI(+)) m/e 451 (M+H)+.


Example 566
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-1-ylcarbonyl)benzamide

The title compound was prepared as described in Example 1A, substituting piperidine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.18 (t, J=5.9 Hz, 1H), 8.49 (d, J=7.0 Hz, 1H), 7.96 (m, 2H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.47 (m, 2H), 7.40 (s, 1H), 6.86 (dd, J=7.0, 1.7 Hz, 1H), 4.52 (d, J=5.9 Hz, 2H), 3.59 (m, 2H), 3.24 (m, 2H), 1.66-1.38 (m, 6H); MS (ESI(+)) m/e 363 (M+H)+.


Example 567
4-[1-(ethylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 557C, substituting ethane sulfonyl chloride for propane-2-sulfonyl chloride. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.10 (t, J=6.0 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.93 (m, 2H), 7.88 (m, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.49 (m, 2H), 7.39 (s, 1H), 6.86 (dd, J=7.0, 1.6 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.23 (m, 2H), 3.95 (m, 3H), 3.19 (q, J=7.3 Hz, 2H), 1.25 (t, J=7.3 Hz, 3H); MS (ESI(+)) m/e 399 (M+H)+.


Example 568
4-[1-(cyclopropylsulfonyl)azetidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 557C, substituting cyclopropane sulfonyl chloride for propane-2-sulfonyl chloride. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.10 (t, J=6.0 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.93 (m, 2H), 7.88 (m, 1H), 7.52 (d, J=1.1 Hz, 1H), 7.50 (m, 2H), 7.39 (s, 1H), 6.86 (dd, J=7.0, 1.6 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.26 (t, J=7.7 Hz, 2H), 3.99 (m, 3H), 2.85 (m, 1H), 1.06 (m, 2H), 0.97 (m, 2H); MS (ESI(+)) m/e 411 (M+H)+.


Example 569
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)azetidin-3-yl]benzamide

The title compound was prepared as described in Example 557C, substituting benzene sulfonyl chloride for propane-2-sulfonyl chloride. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.04 (t, J=5.9 Hz, 1H), 8.47 (m, 1H), 7.92-7.82 (m, 4H), 7.75 (m, 4H), 7.51 (d, J=1.2 Hz, 1H), 7.36 (s, 1H), 7.97 (m, 2H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 4.47 (d, J=5.9 Hz, 2H), 4.16 (m, 2H), 3.79 (m, 1H), 3.67 (m, 2H); MS (ESI(+)) m/e 447 (M+H)+.


Example 570
propan-2-yl-4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate

To a suspension N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide (0.103 g, 0.249 mmol) in dichloromethane (2 ml) was added N-methylmorpholine (0.110 ml, 0.997 mmol) followed by isopropylchloroformate (0.374 ml, 0.374 mmol). A second portion of isopropylchloroformate (0.4 ml) was added and after 1 hour the mixture was directly purified by normal phase chromatography to give the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.05 (t, J=6.0 Hz, 1H), 8.51 (d, J=7.0 Hz, 1H), 7.92 (s, 1H), 7.68 (d, J=3.8 Hz, 1H), 7.56 (d, J=1.2 Hz, 1H), 7.40 (d, J=1.4 Hz, 1H), 6.96 (d, J=3.8 Hz, 1H), 6.88 (dd, J=7.0, 1.7 Hz, 1H), 4.78 (hept, J=6.2 Hz, 1H), 4.47 (d, J=5.9 Hz, 2H), 4.05 (d, J=12.9 Hz, 2H), 3.10-2.97 (m, 1H), 2.98-2.81 (m, 2H), 2.01-1.88 (m, 2H), 1.57-1.38 (m, 2H), 1.19 (d, J=6.2 Hz, 6H); MS (ESI(+)) m/e 427 (M+H)+.


Example 571
2-methylpropyl 4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}piperidine-1-carboxylate

The title compound was prepared as described in Example 570, substituting isobutyl carbonochloridate for isopropyl carbonochloridate. 1H NMR (300 MHz, DMSO-d6) δ 8.99 (t, J=6.0 Hz, 1H), 8.48 (dd, J=7.0, 0.9 Hz, 1H), 7.88 (t, J=1.0 Hz, 1H), 7.67 (d, J=3.9 Hz, 1H), 7.51 (d, J=1.1 Hz, 1H), 7.37 (s, 1H), 6.96 (d, J=3.1 Hz, 1H), 6.82 (dd, J=7.0, 1.8 Hz, 1H), 4.46 (d, J=5.8 Hz, 2H), 4.06 (d, J=13.3 Hz, 2H), 3.79 (d, J=6.6 Hz, 2H), 3.13-2.97 (m, 1H), 2.97-2.80 (m, 2H), 2.03-1.77 (m, 3H), 1.48 (qd, J=12.5, 4.2 Hz, 2H), 0.89 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 441 (M+H)+.


Example 572
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 3,3,3-trifluoropropanoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.00 (t, J=6.0 Hz, 1H), 8.48 (dd, J=6.9, 1.0 Hz, 1H), 7.88 (t, J=1.0 Hz, 1H), 7.67 (d, J=3.8 Hz, 1H), 7.51 (d, J=1.3 Hz, 1H), 7.40-7.33 (m, 1H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.46 (d, J=6.3 Hz, 2H), 3.90 (d, J=13.8 Hz, 1H), 3.66 (q, J=11.0 Hz, 2H), 3.23-3.04 (m, 2H), 2.71 (td, J=12.8, 2.6 Hz, 1H), 2.07-1.88 (m, 2H), 1.71-1.31 (m, 2H); MS (ESI(+)) m/e 451 (M+H)+.


Example 573
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]piperidin-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2-methylpropane-1-sulfonyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=6.0 Hz, 1H), 8.48 (d, J=6.9 Hz, 1H), 7.89 (s, 1H), 7.68 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.1 Hz, 1H), 7.38 (s, 1H), 6.98 (d, J=3.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.46 (d, J=6.0 Hz, 2H), 3.71-3.59 (m, 2H), 2.99 (tt, J=11.6, 3.6 Hz, 1H), 2.94-2.82 (m, 4H), 2.20-2.08 (m, 1H), 2.08-1.97 (m, 2H), 1.62 (qd, J=12.6, 4.1 Hz, 2H), 1.04 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 461 (M+H)+.


Example 574
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 4,4,4-trifluorobutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.00 (t, J=6.0 Hz, 1H), 8.48 (d, J=6.8 Hz, 1H), 7.89 (s, 1H), 7.68 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.41-7.34 (m, 1H), 6.96 (d, J=3.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.54-4.38 (m, 3H), 4.02-3.88 (m, 1H), 3.12 (tdt, J=11.3, 7.9, 3.1 Hz, 2H), 2.76-2.41 (m, 5H), 2.06-1.88 (m, 2H), 1.58 (qd, J=12.3, 4.0 Hz, 1H), 1.42 (qd, J=12.5, 4.2 Hz, 1H); MS (ESI(+)) m/e 465 (M+H)+.


Example 575
N-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide

A solution of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(1-isobutyrylpiperidin-4-yl)benzamide (0.025 g, 0.062 mmol) in chloroform (1.030 ml) was treated with N-chlorosuccinimide (9.49 mg, 0.071 mmol) and the reaction was stirred at ambient temperature for 16 hours. The reaction was concentrated under a stream of warm nitrogen. The residue was purified by normal phase chromatography to give the title compound. 1H NMR (500 MHz, methanol-d4) δ ppm 8.67 (d, J=7.0 Hz, 1H), 8.11 (s, 1H), 7.89-7.83 (m, 2H), 7.81 (s, 1H), 7.57 (dd, J=7.1, 1.5 Hz, 1H), 7.43-7.37 (m, 2H), 4.80-4.75 (m, 2H), 4.75-4.67 (m, 1H), 4.25-4.16 (m, 1H), 3.28-3.18 (m, 1H), 3.07-2.88 (m, 2H), 2.79-2.66 (m, 1H), 2.02-1.85 (m, 2H), 1.75-1.53 (m, 2H), 1.17-1.08 (m, 6H); MS (ESI(+)) m/e 439 (M+H)+.


Example 576
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.02 (t, J=6.0 Hz, 1H), 8.49 (dd, J=7.1, 1.0 Hz, 1H), 8.13 (s, 1H), 7.89 (t, J=1.0 Hz, 1H), 7.81 (s, 1H), 7.74 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.3 Hz, 1H), 7.43-7.36 (m, 1H), 7.23 (d, J=3.8 Hz, 1H), 6.85 (dd, J=7.1, 1.7 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.04 (s, 2H), 3.68 (dt, J=11.8, 4.6 Hz, 2H), 3.52 (ddd, J=11.9, 9.1, 3.0 Hz, 2H), 1.51 (ddd, J=13.4, 9.2, 4.2 Hz, 2H), 1.24 (dt, J=13.4, 4.0 Hz, 2H), 0.96 (s, 3H); MS (ESI(+)) m/e 436 (M+H)+.


Example 577
5-[1-(2-cyano-2-methylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 2,2-dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ 9.05 (t, J=6.0 Hz, 1H), 8.49 (dd, J=6.8, 1.0 Hz, 1H), 8.19 (d, J=0.7 Hz, 1H), 7.92 (s, 1H), 7.90-7.88 (m, 1H), 7.76 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.1 Hz, 1H), 7.43-7.36 (m, 1H), 7.27 (d, J=3.8 Hz, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.48 (d, J=5.7 Hz, 2H), 4.35 (s, 2H), 1.35 (s, 6H); MS (ESI(+)) m/e 405 (M+H)+.


Example 578
4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide
Example 578A
1-(5-bromo-4-chlorothiophen-2-yl)ethanone

2-Bromo-3-chlorothiophene (10.7 g, 51.5 mmol) was dissolved in dichloromethane (73.5 ml). The flask was equipped with a desiccant filled drying tube and the solution was chilled in an ice bath. Acetyl chloride (6.06 g, 77 mmol) was added followed by addition of aluminum trichloride (8.24 g, 61.8 mmol) over about 2 minutes (reaction bubbled vigorously as aluminum trichloride was added). The reaction mixture was stirred overnight, allowing to warm to room temperature, and then added cautiously and with stirring to a 1-L beaker containing ˜200 mL sat sodium bicarbonate. The mixture was stirred for 30 minutes and diluted with dichloromethane (˜100 mL). The layers were separated and the organic layer was washed with aqueous saturated sodium bicarbonate, water, and brine. The combined organic layers were dried with sodium sulfate, filtered, and concentrated to give a crude solid. This material was recrystallized from hot hexanes to give the title compound.


Example 578B
5-bromo-4-chlorothiophene-2-carboxylic acid

Sodium hydroxide (50% in water) (5.82 ml, 110 mmol) was added to water (15 ml), and the mixture was chilled to 0° C. Bromine solution (1.669 ml, 32.6 mmol) was added, followed by dropwise addition of a solution of 1-(5-bromo-4-chlorothiophen-2-yl)ethanone (2.4 g, 10.02 mmol) in dioxane (18 ml). The mixture was stirred for 1.5 hours at room temperature, washed with dichloromethane, and then the aqueous phase was adjusted to pH 1 using 4N aqueous HCl. The precipitated solid was collected by filtration to give the title compound.


Example 578C
4-chloro-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 51A, substituting 5-bromo-4-chlorothiophene-2-carboxylic acid for 4-bromoaniline.


Example 578D
4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-chloro-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.17 (t, J=5.9 Hz, 1H), 8.50 (d, J=7.0 Hz, 1H), 8.31 (s, 1H), 7.93-7.88 (m, 2H), 7.83 (s, 1H), 7.53 (d, J=1.1 Hz, 1H), 7.42 (s, 1H), 6.85 (dd, J=7.0, 1.6 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 3.98 (d, J=7.2 Hz, 2H), 2.20-2.08 (m, 1H), 0.86 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 414 (M+H)+.


Example 579
4-chloro-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(3R)-tetrahydrofuran-3-ylmethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and (R)-4-chloro-5-(1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.17 (t, J=6.0 Hz, 1H), 8.50 (d, J=7.0 Hz, 1H), 8.28 (s, 1H), 7.93-7.88 (m, 2H), 7.83 (s, 1H), 7.53 (d, J=1.2 Hz, 1H), 7.42 (s, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.28-4.15 (m, 3H), 3.78-3.72 (m, 1H), 3.67-3.61 (m, 1H), 1.98-1.90 (m, 1H), 1.84-1.70 (m, 2H), 1.65-1.57 (m, 1H); MS (ESI(+)) m/e 442 (M+H)+.


Example 621
5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide
Example 621A
N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromothiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 5-bromothiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 621B
5-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 2-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromothiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.9 Hz, 1H), 8.88 (s, 1H), 8.48 (s, 1H), 8.04 (d, J=0.5 Hz, 1H), 7.84 (dd, J=9.2, 0.7 Hz, 1H), 7.79 (d, J=0.5 Hz, 1H), 7.71 (d, J=3.9 Hz, 1H), 7.66 (dd, J=9.2, 1.7 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 4.72 (s, 1H), 4.54 (d, J=5.8 Hz, 2H), 4.03 (s, 2H), 1.08 (s, 6H); MS (ESI(+)) m/e 397 (M+H)+.


Example 622
5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromothiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.9 Hz, 1H), 8.88 (s, 1H), 8.48 (s, 1H), 8.04 (d, J=0.5 Hz, 1H), 7.84 (dd, J=9.2, 0.7 Hz, 1H), 7.79 (d, J=0.5 Hz, 1H), 7.71 (d, J=3.9 Hz, 1H), 7.66 (dd, J=9.2, 1.7 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 4.72 (s, 1H), 4.54 (d, J=5.8 Hz, 2H), 4.03 (s, 2H), 1.08 (s, 6H); MS (ESI(+)) m/e 437 (M+H)+.


Example 623
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)azetidin-3-yl]benzamide

The title compound was prepared as described in Example 557C, substituting methane sulfonyl chloride for propane-2-sulfonyl chloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.11 (t, J=6.0 Hz, 1H), 8.49 (m, 1H), 7.91 (m, 2H), 7.88 (m, 1H), 7.52 (m, 2H), 7.49 (m, 1H), 7.39 (s, 1H), 6.86 (dd, J=7.0, 1.7 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.23 (m, 2H), 3.95 (m, 3H), 3.08 (s, 3H); MS (ESI(+)) m/e 385 (M+H)+.


Example 624
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(methylsulfonyl)pyrrolidin-3-yl]benzamide

The title compound was prepared as described in Example 557C, substituting methane sulfonyl chloride for propane-2-sulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (m, 3H), 7.52 (d, J=1.2 Hz, 1H), 7.45 (m, 2H), 7.38 (m, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 3.73 (dd, J=9.6, 7.5 Hz, 1H), 3.47 (m, 2H), 3.35 (m, 1H), 3.19 (t, J=9.6 Hz, 1H), 2.97 (s, 3H), 2.31 (m, 1H), 2.02 (m, 1H); MS (ESI(+)) m/e 399 (M+H)+.


Example 625
4-[1-(ethylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 557C, substituting ethane sulfonyl chloride for propane-2-sulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (m, 3H), 7.52 (d, J=1.2 Hz, 1H), 7.45 (m, 2H), 7.38 (s, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.50 (d, J=5.9 Hz, 2H), 3.75 (dd, J=9.5, 7.5 Hz, 1H), 3.50 (m, 2H), 3.38 (m, 1H), 3.26-3.12 (m, 3H), 2.32 (m, 1H), 2.03 (m, 1H), 1.24 (t, J=7.3 Hz, 3H); MS (ESI(+)) m/e 413 (M+H)+.


Example 626
4-[1-(cyclopropylsulfonyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 557C, substituting cyclopropane sulfonyl chloride for propane-2-sulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (m, 3H), 7.51 (d, J=1.2 Hz, 1H), 7.45 (m, 2H), 7.38 (m, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.50 (d, J=5.9 Hz, 2H), 3.79 (dd, J=9.7, 7.5 Hz, 1H), 3.53 (m, 2H), 3.43 (m, 1H), 3.23 (m, 1H), 2.78 (m, 1H), 2.34 (m, 1H), 2.01 (m, 1H), 0.98 (m, 4H); MS (ESI(+)) m/e 425 (M+H)+.


Example 627
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)pyrrolidin-3-yl]benzamide

The title compound was prepared as described in Example 557C, substituting benzene sulfonyl chloride for propane-2-sulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.04 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.87 (m, 3H), 7.81 (m, 2H), 7.74 (m, 1H), 7.66 (m, 2H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (m, 1H), 7.25 (m, 2H), 6.84 (dd, J=6.9, 1.7 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 3.72 (dd, J=9.8, 7.5 Hz, 1H), 3.46 (m, 1H), 3.26 (m, 2H), 3.11 (m, 1H), 2.17 (m, 1H), 1.78 (m, 1H); MS (ESI(+)) m/e 461 (M+H)+.


Example 672
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)pyrrolidin-3-yl]benzamide

The title compound was prepared as described in Example 557C, substituting propane-2-sulfonyl chloride for propane-2-sulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide. 1H NMR (501 MHz, DMSO-d6) δ ppm 9.04 (t, J=6.0 Hz, 1H), 8.47 (d, J=6.9 Hz, 1H), 7.87 (m, 3H), 7.50 (d, J=1.2 Hz, 1H), 7.43 (m, 2H), 7.37 (s, 1H), 6.84 (dd, J=7.0, 1.6 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 3.77 (m, 1H), 3.52 (m, 2H), 3.42 (m, 2H), 3.25 (m, 1H), 2.30 (m, 1H), 2.04 (m, 1H), 1.25 (dd, J=6.8, 1.4 Hz, 6H); MS (ESI(+)) m/e 427 (M+H)+.


Example 673
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]phenyl}urea

The title compound was prepared as described in Example 51A, substituting 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 4-bromoaniline. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.66 (s, 1H), 8.50 (d, J=7.0 Hz, 1H), 8.01 (s, 1H), 7.90 (s, 1H), 7.77 (s, 1H), 7.54 (s, 1H), 7.40 (m, 5H), 6.87 (dd, J=7.0, 1.6 Hz, 1H), 6.71 (t, J=6.0 Hz, 1H), 4.34 (d, J=6.0 Hz, 2H), 4.23 (t, J=5.3 Hz, 2H), 3.69 (t, J=5.3 Hz, 2H), 3.23 (s, 3H); MS (ESI(+)) m/e 391 (M+H)+.


Example 674
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea

The title compound was prepared as described in Example 51A, substituting 1-(tetrahydrofuran-2-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 4-bromoaniline. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.64 (s, 1H), 8.47 (d, J=7.0 Hz, 1H), 8.00 (s, 1H), 7.87 (s, 1H), 7.77 (s, 1H), 7.50 (d, J=1.2 Hz, 1H), 7.40 (m, 5H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.70 (t, J=6.0 Hz, 1H), 4.33 (d, J=6.0 Hz, 2H), 4.13 (m, 3H), 3.74 (m, 1H), 3.62 (m, 1H), 1.91 (m, 1H), 1.76 (m, 2H), 1.60 (m, 1H); MS (ESI(+)) m/e 417 (M+H)+.


Example 675
1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-{4-[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]phenyl}urea

The title compound was prepared as described in Example 51A, substituting 1-(tetrahydro-2H-pyran-4-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-(4-bromophenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 4-bromoaniline. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.64 (s, 1H), 8.47 (d, J=7.0 Hz, 1H), 8.02 (s, 1H), 7.87 (s, 1H), 7.77 (d, J=0.8 Hz, 1H), 7.50 (d, J=1.2 Hz, 1H), 7.40 (m, 5H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.70 (t, J=6.0 Hz, 1H), 4.32 (d, J=5.9 Hz, 2H), 3.98 (d, J=7.1 Hz, 2H), 3.81 (m, 2H), 3.23 (m, 2H), 2.05 (m, 1H), 1.40 (m, 2H), 1.23 (m, 2H); MS (ESI(+)) m/e 431 (M+H)+.


Example 676
5-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-((1,4-dioxan-2-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromothiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.9 Hz, 1H), 8.90-8.85 (m, 1H), 8.48 (s, 1H), 8.12 (s, 1H), 7.84 (dd, J=9.2, 0.8 Hz, 1H), 7.82 (d, J=0.6 Hz, 1H), 7.71 (d, J=3.9 Hz, 1H), 7.66 (dd, J=9.2, 1.7 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 4.54 (d, J=5.8 Hz, 2H), 4.20-4.12 (m, 2H), 3.95-3.83 (m, 1H), 3.74 (dd, J=11.4, 2.5 Hz, 2H), 3.68-3.60 (m, 1H), 3.59-3.39 (m, 2H), 3.29-3.21 (m, 1H); MS (ESI(+)) m/e 425 (M+H)+.


Example 677
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.00 (t, J=6.0 Hz, 1H), 8.48 (dd, J=7.0, 0.8 Hz, 1H), 7.91-7.85 (m, 1H), 7.67 (d, J=3.8 Hz, 1H), 7.55-7.35 (m, 4H), 7.34-7.25 (m, 2H), 6.98 (dd, J=3.8, 0.5 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.60 (d, J=13.2 Hz, 1H), 4.46 (d, J=5.9 Hz, 2H), 3.45 (d, J=12.7 Hz, 1H), 3.28-3.08 (m, 2H), 2.93 (td, J=12.8, 2.5 Hz, 1H), 2.00 (dd, J=43.2, 12.5 Hz, 2H), 1.68-1.39 (m, 2H); MS (ESI(+)) m/e 463 (M+H)+.


Example 678
tert-butyl 4-{4-[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.00-8.96 (m, 1H), 8.51-8.46 (m, 1H), 8.04-8.00 (m, 1H), 7.89-7.81 (m, 2H), 7.81-7.77 (m, 1H), 7.39-7.32 (m, 2H), 4.68 (s, 2H), 4.27-4.16 (m, 2H), 2.97-2.70 (m, 3H), 1.92-1.78 (m, 2H), 1.71-1.50 (m, 2H), 1.48 (s, 9H); MS (ESI(+)) m/e 436 (M+H)+.


Example 679
4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.19 (d, J=0.9 Hz, 1H), 8.65 (d, J=1.2 Hz, 1H), 8.20 (d, J=1.1 Hz, 1H), 8.03 (d, J=1.5 Hz, 1H), 7.90-7.83 (m, 2H), 7.73-7.66 (m, 2H), 4.74 (s, 2H), 2.44-2.22 (m, 3H), 1.92-1.76 (m, 2H), 1.76-1.49 (m, 4H), 1.35-1.14 (m, 2H); MS (ESI(+)) m/e 378 (M+H)+.


Example 680
tert-butyl 4-(4-{[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyrazin-6-ylmethanamine for imidazo[1,2-a]pyridin-6-amine. 1H NMR (500 MHz, methanol-d4) δ ppm 8.99-8.95 (m, 1H), 8.48-8.44 (m, 1H), 8.02 (s, 1H), 7.81-7.77 (m, 1H), 7.33-7.26 (m, 2H), 7.15-7.09 (m, 2H), 4.49 (s, 2H), 4.22-4.14 (m, 2H), 2.92-2.73 (m, 2H), 2.74-2.58 (m, 1H), 1.82-1.74 (m, 2H), 1.61-1.41 (m, 11H); MS (ESI(+)) m/e 451 (M+H)+.


Example 681
2-cyclopentyl-N-(4-{[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]amino}phenyl)acetamide

The title compound was prepared as described in Example 1C, substituting N-(4-aminophenyl)-2-cyclopentylacetamide for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyrazin-6-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (500 MHz, methanol-d4) δ ppm 9.17-9.13 (m, 1H), 8.60 (s, 1H), 8.18 (s, 1H), 7.99 (d, J=1.5 Hz, 1H), 7.46-7.40 (m, 2H), 7.35-7.29 (m, 2H), 4.56 (bs, 2H), 2.37-2.23 (m, 3H), 1.90-1.77 (m, 2H), 1.77-1.49 (m, 4H), 1.34-1.17 (m, 2H); MS (ESI(+)) m/e 393 (M+H)+.


Example 682
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide

A solution of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide (0.05 g, 0.150 mmol) in tetrahydrofuran (1.246 ml) was treated with sodium hydride (0.018 g, 0.449 mmol) in 3 portions. The reaction was stirred at ambient temperature for 45 minutes and became a partially homogeneous solution. Benzenesulfonyl chloride (0.021 ml, 0.164 mmol) was added and the mixture was stirred for 16 hours. The reaction was treated with 0.1 mL water and was concentrated under a stream of nitrogen. Reverse-phase chromatography provided the title compound. 1H NMR (500 MHz, methanol-d4) δ ppm 8.73 (dd, J=7.0, 0.9 Hz, 1H), 8.15 (dd, J=2.2, 0.8 Hz, 1H), 7.97 (d, J=2.2 Hz, 1H), 7.89-7.75 (m, 5H), 7.73-7.59 (m, 3H), 7.46 (dd, J=7.0, 1.6 Hz, 1H), 7.37-7.31 (m, 2H), 4.75 (s, 2H), 3.96-3.88 (m, 2H), 2.67-2.52 (m, 1H), 2.48-2.37 (m, 2H), 1.95-1.72 (m, 4H); MS (ESI(+)) m/e 475 (M+H)+.


Example 683
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 682, substituting propane-2-sulfonyl chloride for benzenesulfonyl chloride. 1H NMR (500 MHz, methanol-d4) δ ppm 8.75 (d, J=7.0 Hz, 1H), 8.17 (d, J=2.2 Hz, 1H), 7.99 (d, J=2.2 Hz, 1H), 7.89-7.83 (m, 2H), 7.80 (s, 1H), 7.49 (dd, J=7.0, 1.6 Hz, 1H), 7.43-7.37 (m, 2H), 4.77 (s, 2H), 3.95-3.87 (m, 2H), 3.38-3.29 (m, 1H), 3.12-3.00 (m, 2H), 2.89-2.75 (m, 1H), 1.95-1.86 (m, 2H), 1.82-1.68 (m, 2H), 1.34 (d, J=6.8 Hz, 6H); MS (ESI(+)) m/e 417 (M+H)+.


Example 684
4-[1-(cyclopropylsulfonyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide

The title compound was prepared as described in Example 682, substituting cyclopropanesulfonyl chloride for benzenesulfonyl chloride. 1H NMR (500 MHz, methanol-d4) δ ppm 8.75 (dd, J=7.0, 0.9 Hz, 1H), 8.19-8.15 (m, 1H), 7.98 (d, J=2.2 Hz, 1H), 7.90-7.84 (m, 2H), 7.80 (s, 1H), 7.48 (dd, J=7.0, 1.6 Hz, 1H), 7.45-7.38 (m, 2H), 4.77 (s, 2H), 3.92-3.84 (m, 2H), 3.07-2.96 (m, 2H), 2.86-2.73 (m, 1H), 2.57-2.46 (m, 1H), 2.00-1.91 (m, 2H), 1.88-1.73 (m, 2H), 1.13-0.99 (m, 4H); MS (ESI(+)) m/e 439 (M+H)+.


Example 685
5-{(1R)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 685A
tert-butyl 5-formylthiophene-2-carboxylate

5-Formylthiophene-2-carboxylic acid (5.3 g, 33.9 mmol) was taken up in tetrahydrofuran (100 ml) and boc-anhydride (16.30 g, 74.7 mmol) was added, followed by N,N-dimethylaminopyridine (0.829 g, 6.79 mmol). The mixture was stirred overnight at room temperature, during which time the reaction became a dark, purplish color. It was diluted with sat sodium bicarbonate and extracted with ether. The organic layers were dried sodium sulfate, concentrated then purified by normal phase chromatography to give the title compound.


Example 685B
(S,E)-tert-butyl 5-(((tert-butylsulfinyl)imino)methyl)thiophene-2-carboxylate

tert-Butyl 5-formylthiophene-2-carboxylate (2 g, 9.42 mmol) and (S)-2-methylpropane-2-sulfinamide (1.370 g, 11.31 mmol) were dissolved in dichloromethane (100 ml). The mixture was chilled in an ice bath to which was added tetraethoxytitanium (8.7 ml, 41.5 mmol). The mixture was allowed to warm to room temperature overnight with stirring. The mixture was poured into a large Erlenmeyer flask with 200 mL dichloromethane and was diluted with 18 mL H2O. After vigorous stirring for 30 minutes the suspension was filtered through diatomaceous earth and the filtrate was concentrated. Purification using normal phase chromatography provided the title compound.


Example 685C
tert-butyl 5-((R)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate and tert-butyl 5-((S)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate

(S,E)-tert-Butyl 5-((tert-butylsulfinylimino)methyl)thiophene-2-carboxylate (1 g, 3.17 mmol) was dissolved in dichloromethane (15.85 ml) and chilled to −45° C. in an acetone bath to which dry ice had been added to achieve the desired temperature. Isobutylmagnesium bromide (2.0M in diethyl ether; 3.17 ml, 6.34 mmol) was added dropwise over 5 minutes. The mixture was stirred for 4 hours keeping the temperature between −40° C. and −50° C. by periodic addition of dry ice and then warmed to room temperature overnight. The mixture was quenched with saturated ammonium chloride (exothermic, bubbling) and extracted with dichloromethane (three times; considerable emulsion formed). The organic extracts were dried with sodium sulfate, filtered, concentrated and chromatographed to provide both tert-butyl 5-((R)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate and tert-butyl 5-((S)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate as separate compounds.


Example 685D
(R)-tert-butyl 5-(1-amino-3-methylbutyl)thiophene-2-carboxylate

The title compound was prepared as described in Example 324C, substituting tert-butyl 5-((R)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate for tert-butyl 5-((R)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate.


Example 685E
(R)-5-(1-(cyclopropanecarboxamido)-3-methylbutyl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 1A, substituting (R)-tert-butyl 5-(1-amino-3-methylbutyl)thiophene-2-carboxylate for 3-methylbutan-1-amine and cyclopropanecarboxylic acid for 4-nitrobenzoic acid followed by acidic deprotection as described in Example 28A, substituting (R)-tert-butyl 5-(1-(cyclopropanecarboxamido)-3-methylbutyl)thiophene-2-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 685F
5-{(1R)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and (R)-5-(1-(cyclopropanecarboxamido)-3-methylbutyl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.00 (t, J=6.0 Hz, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.48 (d, J=7.4 Hz, 1H), 7.88 (d, J=1.1 Hz, 1H), 7.64 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 6.98 (d, J=3.8 Hz, 1H), 6.82 (dd, J=7.0, 1.7 Hz, 1H), 5.11 (td, J=8.8, 5.0 Hz, 1H), 4.46 (d, J=5.9 Hz, 2H), 1.80-1.52 (m, 4H), 0.95-0.83 (m, 6H), 0.75-0.59 (m, 4H); MS (ESI(+)) m/e 411 (M+H)+.


Example 686
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{(1R)-3-methyl-1-[(tetrahydrofuran-3-ylacetyl)amino]butyl}thiophene-2-carboxamide

The title compound was described as in Example 685, substituting 2-(tetrahydrofuran-3-yl)acetic acid for cyclopropanecarboxylic acid in Example 685E. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.00 (t, J=6.0 Hz, 1H), 8.48 (d, J=7.0 Hz, 1H), 8.39 (d, J=8.5 Hz, 1H), 7.88 (s, 1H), 7.64 (d, J=3.7 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 6.97 (d, J=3.8 Hz, 1H), 6.82 (dd, J=7.0, 1.7 Hz, 1H), 5.16-5.05 (m, 1H), 4.45 (d, J=5.9 Hz, 2H), 3.76-3.51 (m, 3H), 3.29-3.21 (m, 1H), 2.29-2.16 (m, 3H), 2.02-1.86 (m, 1H), 1.78-1.40 (m, 4H), 0.99-0.77 (m, 6H); MS (ESI(+)) m/e 455 (M+H)+.


Example 687
5-{(1S)-1-[(cyclopropylcarbonyl)amino]-3-methylbutyl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was described as in Example 685, substituting butyl 5-((S)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate for tert-butyl 5-((R)-1-((S)-1,1-dimethylethylsulfinamido)-3-methylbutyl)thiophene-2-carboxylate in Example 685D. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04-8.96 (m, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.48 (dd, J=7.0, 0.9 Hz, 1H), 7.88 (s, 1H), 7.64 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.1 Hz, 1H), 7.37 (s, 1H), 6.98 (d, J=3.8 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 5.17-5.05 (m, 1H), 4.46 (d, J=5.9 Hz, 2H), 1.77-1.44 (m, 4H), 1.01-0.77 (m, 6H), 0.66 (d, J=7.2 Hz, 4H); MS (ESI(+)) m/e 411 (M+H)+.


Example 688
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1-phenylpiperidin-4-yl)-1,3-thiazole-5-carboxamide
Example 688A
ethyl 2-(piperidin-4-yl)thiazole-5-carboxylate

Ethyl 3-ethoxyacrylate (1.50 g, 10.38 mml) was dissolved in dioxane/water and chilled to −10° C. N-Bromosuccinimide (2.03 g, 11.42 mmol) was added and the mixture was stirred 1 hour at room temperature. tert-Butyl 4-carbamothioylpiperidine-1-carboxylate (2.54 g, 10.38 mmol) was added and the mixture was heated at 100° C. for 1 hour. The reaction mixture was poured into 25 mL saturated ammonium hydroxide and extracted with dichloromethane. The combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. Normal phase chromatography provided the title compound.


Example 688B
ethyl 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate

Ethyl 2-(piperidin-4-yl)thiazole-5-carboxylate (100 mg, 0.416 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (21 mg, 0.033 mmol), bis(dibenzylideneacetone)palladium(0) (15 mg, 0.017 mmol) and cesium carbonate (678 mg, 2.081 mmol) were placed in a pressure tube capped with a septum and degassed with nitrogen by passing a stream through the vessel for 30 minutes. Separately, bromobenzene (68.6 mg, 0.437 mmol) was dissolved in toluene (2 ml) and the solution was degassed by bubbling nitrogen for 30 minutes. The bromobenzene solution was added to the solid mixture and the sealed tube was heated to 100° C. overnight. The mixture was partitioned between dichloromathane and water and the combined organic layers were concentrated and purified by normal phase chromatography to give the title compound.


Example 688C
lithium 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate

A solution of ethyl 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate (31 mg, 0.098 mmol) in 1 ml of 1:1 tetrahydrofuran/methanol was treated with 1M aqueous LiOH (0.11 ml, 0.11 mol) and stirred at 65° C. for 3 hours. The mixture was taken to dryness and used directly in the next step.


Example 688D
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(1-phenylpiperidin-4-yl)-1,3-thiazole-5-carboxamide

Lithium 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate (28.8 mg, 0.098 mmol), imidazo[1,2-a]pyridin-7-ylmethanamine (17.31 mg, 0.118 mmol), 4-methylmorpholine (49.6 mg, 0.490 mmol) and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (55.9 mg, 0.147 mmol) were combined in a vial with dichloromethane (2.5 ml) and the reaction was stirred overnight. The mixture was partitioned between dichloromethane and saturated sodium bicarbonate. The organic layers were dried with sodium sulfate, filtered, and concentrated. Trituration of the crude material with dichloromethane provided the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.21 (t, J=5.9 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 8.34 (s, 1H), 7.91-7.88 (m, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.43-7.38 (m, 1H), 7.26-7.16 (m, 2H), 7.01-6.93 (m, 2H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.81-6.72 (m, 1H), 4.48 (d, J=5.9 Hz, 2H), 3.81-3.73 (m, 2H), 3.24-3.01 (m, 1H), 2.90-2.78 (m, 2H), 2.19-2.09 (m, 2H), 1.90-1.73 (m, 2H); MS (ESI(+)) m/e 418 (M+H)+.


Example 697
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(pyridin-2-yl)piperidin-4-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 688, substituting 2-bromopyridine for bromobenzene in Example 688B. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.21 (t, J=5.9 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.33 (s, 1H), 8.13-8.09 (m, 1H), 7.89 (s, 1H), 7.55-7.48 (m, 2H), 7.40 (s, 1H), 6.86 (d, J=8.7 Hz, 1H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.61 (dd, J=6.9, 5.1 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.40-4.32 (m, 2H), 3.03-2.92 (m, 2H), 2.14-2.05 (m, 2H), 1.68 (qd, J=12.5, 3.9 Hz, 2H); MS (ESI(+)) m/e 419 (M+H)+.


Example 698
5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-fluorotetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=6.0 Hz, 1H), 8.49 (d, J=7.1 Hz, 1H), 8.11 (s, 1H), 7.89 (s, 1H), 7.85 (s, 1H), 7.75 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.26 (d, J=3.9 Hz, 1H), 6.85 (dd, J=7.0, 1.6 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.42 (d, J=21.4 Hz, 2H), 3.74 (ddd, J=11.4, 4.6, 2.9 Hz, 2H), 3.51 (td, J=11.3, 2.0 Hz, 2H), 1.92-1.64 (m, 2H), 1.55 (t, J=11.8 Hz, 2H); MS (ESI(+)) m/e 440 (M+H)+.


Example 734
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide
Example 734A
5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-bromofuran-2-carboxylic acid for 4-nitrobenzoic acid.


Example 734B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and bromide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.89 (t, J=6.1 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 8.13 (d, J=0.5 Hz, 1H), 7.91-7.86 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.17 (d, J=3.6 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.67 (d, J=3.5 Hz, 1H), 4.49 (d, J=6.0 Hz, 2H), 4.07 (s, 2H), 3.68 (dt, J=11.5, 4.5 Hz, 2H), 3.51 (ddd, J=11.9, 9.3, 3.0 Hz, 2H), 1.51 (ddd, J=13.4, 9.2, 4.2 Hz, 2H), 1.33-1.15 (m, 2H), 0.96 (s, 3H); MS (ESI(+)) m/e 420 (M+H)+.


Example 735
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide
Example 735A
tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)furan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline.


Example 735B
tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)furan-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)furan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 735C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)furan-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)furan-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 735D
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)-furan-2-carboxamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.85 (t, J=6.1 Hz, 1H), 8.47 (dd, J=7.0, 0.8 Hz, 1H), 7.92-7.83 (m, 1H), 7.55-7.45 (m, 2H), 7.41 (td, J=7.5, 1.5 Hz, 1H), 7.37 (s, 1H), 7.34-7.25 (m, 2H), 7.06 (d, J=3.4 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 6.33 (dd, J=3.5, 0.7 Hz, 1H), 4.53 (d, J=13.4 Hz, 1H), 4.44 (d, J=6.0 Hz, 2H), 3.44 (d, J=13.0 Hz, 1H), 3.19 (t, J=12.8 Hz, 1H), 3.11-2.90 (m, 2H), 2.09 (d, J=11.0 Hz, 1H), 1.94 (d, J=11.9 Hz, 1H), 1.73-1.42 (m, 2H); MS (ESI(+)) m/e 447 (M+H)+.


Example 736
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(piperidin-4-yl)-furan-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.84 (t, J=6.1 Hz, 1H), 8.47 (dd, J=7.0, 0.8 Hz, 1H), 7.94-7.82 (m, 1H), 7.51 (d, J=1.2 Hz, 1H), 7.42-7.33 (m, 1H), 7.05 (d, J=3.4 Hz, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 6.31 (dd, J=3.4, 0.6 Hz, 1H), 4.44 (d, J=6.0 Hz, 3H), 4.06-3.90 (m, 1H), 3.21-3.07 (m, 1H), 3.07-2.77 (m, 2H), 2.77-2.59 (m, 1H), 2.06-1.90 (m, 2H), 1.61-1.37 (m, 2H), 0.99 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 395 (M+H)+.


Example 738
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6). δ ppm 9.21 (t, J=5.9 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.33 (s, 1H), 8.13-8.09 (m, 1H), 7.89 (s, 1H), 7.55-7.48 (m, 2H), 7.40 (s, 1H), 6.86 (d, J=8.7 Hz, 1H), 6.83 (dd, J=7.0, 1.6 Hz, 1H), 6.61 (dd, J=6.9, 5.1 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.40-4.32 (m, 2H), 3.03-2.92 (m, 2H), 2.14-2.05 (m, 2H), 1.68 (qd, J=12.5, 3.9 Hz, 2H); MS (ESI(+)) m/e 390 (M+H)+.


Example 739
2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}acetamide

The title compound was prepared as described in Example 1A, substituting N-(4-aminophenyl)-2-cyclopentylacetamide for 3-methylbutan-1-amine and 2-(imidazo[1,2-a]pyridin-7-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 8.75 (dd, J=6.9, 1.0 Hz, 1H), 8.21-8.16 (m, 1H), 8.01 (d, J=2.1 Hz, 1H), 7.89 (s, 1H), 7.55-7.45 (m, 5H), 3.99 (s, 2H), 2.39-2.24 (m, 3H), 1.91-1.76 (m, 2H), 1.78-1.46 (m, 4H), 1.39-1.15 (m, 2H); MS (ESI(+)) m/e 377 (M+H)+.


Example 740
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6). δ ppm 8.88 (t, J=6.1 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 8.15 (s, 1H), 7.90-7.86 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.17 (d, J=3.5 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.65 (d, J=3.5 Hz, 1H), 4.49 (d, J=6.1 Hz, 2H), 3.95 (d, J=7.2 Hz, 2H), 2.21-2.05 (m, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 364 (M+H)+.


Example 741
5-(1-benzyl-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.92 (t, J=6.1 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.27 (d, J=0.7 Hz, 1H), 7.93 (d, J=0.7 Hz, 1H), 7.89 (t, J=0.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.41-7.23 (m, 6H), 7.17 (d, J=3.5 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.68 (d, J=3.5 Hz, 1H), 5.39 (s, 2H), 4.49 (d, J=6.1 Hz, 2H); MS (ESI(+)) m/e 398 (M+H)+.


Example 742
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-tetrahydro furan-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting (S)-1-((tetrahydrofuran-2-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.94 (t, J=6.1 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.15 (s, 1H), 7.89 (s, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.17 (d, J=3.5 Hz, 1H), 6.86 (dd, J=7.0, 1.7 Hz, 1H), 6.68 (d, J=3.5 Hz, 1H), 4.49 (d, J=6.1 Hz, 2H), 4.28-4.09 (m, 3H), 3.78-3.69 (m, 1H), 3.68-3.55 (m, 1H), 2.01-1.88 (m, 1H), 1.85-1.66 (m, 2H), 1.66-1.54 (m, 1H); MS (ESI(+)) m/e 392 (M+H)+.


Example 743
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-pyrazol-4-yl}furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting (R)-1-((tetrahydrofuran-2-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.94 (t, J=6.1 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.15 (s, 1H), 7.89 (s, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.17 (d, J=3.5 Hz, 1H), 6.86 (dd, J=7.0, 1.7 Hz, 1H), 6.68 (d, J=3.5 Hz, 1H), 4.49 (d, J=6.1 Hz, 2H), 4.28-4.07 (m, 3H), 3.78-3.69 (m, 1H), 3.68-3.59 (m, 1H), 2.01-1.88 (m, 1H), 1.85-1.66 (m, 2H), 1.66-1.54 (m, 1H); MS (ESI(+)) m/e 392 (M+H)+.


Example 744
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide
Example 744A
tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)furan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline.


Example 744B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)furan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 744C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.00 (t, J=5.3 Hz, 1H), 8.49 (dd, J=7.0, 0.7 Hz, 1H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (s, 1H), 7.13 (d, J=3.5 Hz, 1H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.58 (d, J=3.0 Hz, 1H), 6.53 (s, 1H), 4.47 (d, J=6.1 Hz, 2H), 4.25 (s, 1H), 4.13 (s, 1H), 3.66 (dd, J=12.2, 6.1 Hz, 2H), 3.01-2.82 (m, 1H), 2.47 (bs, 1H), 2.36 (bs, 1H), 1.09-0.86 (m, 6H); MS (ESI(+)) m/e 393 (M+H)+.


Example 745
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.00 (dd, J=8.8, 5.7 Hz, 1H), 8.49 (dd, J=7.0, 0.5 Hz, 1H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (s, 1H), 7.13 (dd, J=3.4, 2.1 Hz, 1H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.58 (dd, J=6.2, 3.5 Hz, 1H), 6.52 (d, J=15.2 Hz, 1H), 4.47 (d, J=6.1 Hz, 2H), 4.17 (dd, J=21.3, 2.5 Hz, 2H), 3.74-3.53 (m, 2H), 2.45 (bs, 1H), 2.37 (bs, 1H), 2.27 (d, J=7.0 Hz, 1H), 2.22 (d, J=6.9 Hz, 1H), 2.06-1.94 (m, 1H), 0.91 (dd, J=6.5, 5.3 Hz, 6H); MS (ESI(+)) m/e 407 (M+H)+.


Example 746
5-(1-benzoyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6). δ ppm 8.62 (t, J=5.4 Hz, 1H), 8.44-8.39 (m, 1H), 7.81 (s, 1H), 7.51-7.35 (m, 7H), 7.08 (d, J=3.5 Hz, 1H), 6.82 (dd, J=7.0, 1.6 Hz, 1H), 6.53 (d, J=3.5 Hz, 1H), 6.50-6.43 (m, 1H), 4.47 (d, J=6.1 Hz, 2H), 4.20 (d, J=2.1 Hz, 2H), 3.64 (t, J=5.3 Hz, 2H), 2.52-2.46 (m, 2H); MS (ESI(+)) m/e 427 (M+H)+.


Example 747
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[4-(2-methylpropyl)phenyl]furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 4-isobutylphenylboronic acid for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.08 (t, J=6.1 Hz, 1H), 8.49 (dd, J=6.9, 0.8 Hz, 1H), 7.92-7.87 (m, 1H), 7.87-7.79 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.45-7.38 (m, 1H), 7.25 (d, J=8.3 Hz, 2H), 7.21 (d, J=3.6 Hz, 1H), 7.04 (d, J=3.6 Hz, 1H), 6.87 (dd, J=7.0, 1.7 Hz, 1H), 4.51 (d, J=6.0 Hz, 2H), 2.49-2.46 (m, 2H), 1.86 (dp, J=13.4, 6.8 Hz, 1H), 0.87 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 374 (M+H)+.


Example 748
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and (2S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6). δ ppm 9.00 (t, J=5.0 Hz, 1H), 8.49 (dd, J=7.0, 0.6 Hz, 1H), 7.89 (s, 1H), 7.52 (d, J=1.1 Hz, 1H), 7.39 (s, 1H), 7.13 (d, J=3.5 Hz, 1H), 6.84 (dd, J=7.0, 1.6 Hz, 1H), 6.61-6.56 (m, 1H), 6.53 (d, J=9.8 Hz, 1H), 4.47 (d, J=6.1 Hz, 2H), 4.35-4.07 (m, 2H), 3.75-3.58 (m, 2H), 2.90-2.62 (m, 1H), 2.48-2.30 (m, 2H), 1.57 (dt, J=24.3, 8.8 Hz, 1H), 1.32 (dt, J=13.1, 6.8 Hz, 1H), 0.99 (dd, J=9.6, 6.8 Hz, 3H), 0.81 (q, J=7.1 Hz, 3H); MS (ESI(+)) m/e 407 (M+H)+.


Example 749
5-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and 3,3-dimethylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.00 (t, J=6.1 Hz, 1H), 8.49 (dd, J=7.0, 0.7 Hz, 1H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (s, 1H), 7.13 (t, J=3.4 Hz, 1H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.57 (dd, J=6.1, 3.6 Hz, 1H), 6.51 (d, J=23.1 Hz, 1H), 4.47 (d, J=6.0 Hz, 2H), 4.19 (dd, J=31.4, 2.4 Hz, 2H), 3.73-3.62 (m, 2H), 2.41 (d, J=31.8 Hz, 2H), 2.28 (d, J=17.4 Hz, 2H), 0.99 (d, J=7.2 Hz, 9H); MS (ESI(+)) m/e 421 (M+H)+.


Example 750
5-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and cyclopropylacetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05-8.93 (m, 1H), 8.49 (dd, J=7.0, 0.8 Hz, 1H), 7.90-7.87 (m, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (bs, 1H), 7.13 (d, J=3.5 Hz, 1H), 6.84 (dd, J=7.0, 1.6 Hz, 1H), 6.58 (dd, J=6.9, 3.5 Hz, 1H), 6.55-6.48 (m, 1H), 4.47 (d, J=6.1 Hz, 2H), 4.15 (d, J=8.4 Hz, 2H), 3.63 (dt, J=18.3, 5.7 Hz, 2H), 2.48-2.35 (m, 2H), 2.35-2.27 (m, 2H), 1.03-0.91 (m, 1H), 0.49-0.41 (m, 2H), 0.12 (dq, J=10.2, 5.0 Hz, 2H); MS (ESI(+)) m/e 405 (M+H)+.


Example 751
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{1-[(2-methylpropyl)sulfonyl]pyrrolidin-3-yl}-1,3-thiazole-5-carboxamide
Example 751A
tert-butyl 3-(5-formylthiazol-2-yl)pyrrolidine-1-carboxylate

tert-Butyl 3-carbamothioylpyrrolidine-1-carboxylate (5 g, 21.71 mmol), 2-chloromalonaldehyde (3.70 g, 34.7 mmol) and magnesium carbonate (1.830 g, 21.71 mmol) were combined in dioxane (100 ml). The mixture was heated to 60° C. for 3 hours, stirred overnight at room temperature and then filtered through a pad of diatomaceous earth, rinsing with dichloromethane. The filtrate was concentrated in vacuo and then purified by normal phase chromatography to provide the title compound.


Example 751B
2-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)thiazole-5-carboxylic acid

tert-Butyl 3-(5-formylthiazol-2-yl)pyrrolidine-1-carboxylate (3.65 g, 12.93 mmol) was suspended in water (35 ml) and t-butanol (60 ml). Sodium dihydrogenphosphate (2.094 g, 17.45 mmol) was added, followed by 2-methylbut-2-ene (5.34 ml, 50.4 mmol). After 5 minutes, sodium chlorite (2.92 g, 32.3 mmol) was added in portions over about 5 minutes (mildly exothermic). The reaction was stirred for 1 hour at room temperature, then additional 2-methyl-2-butene (2 mL) was added. After stirring for 2 hours at room temperature, the reaction was concentrated and water (100 mL) was added. The mixture was adjusted to pH 2 by addition of 1N hydrochloric acid, then extracted dichloromethane. The organic extracts were dried over sodium sulfate, filtered and concentrated to provide the title compound.


Example 751C
tert-butyl 3-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiazol-2-yl)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 688D, substituting 2-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)thiazole-5-carboxylic acid for lithium 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate.


Example 751D
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 3-(5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiazol-2-yl)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 751E
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-{1-[(2-methylpropyl)sulfonyl]pyrrolidin-3-yl}-1,3-thiazole-5-carboxamide

N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide, 2.7-trifluoroacetic acid (150 mg, 0.236 mmol) was dissolved in N,N-dimethylformamide (0.7 mL). Triethylamine (0.3 mL, 2.152 mmol) was added, followed by 2-methylpropane-1-sulfonyl chloride (74.0 mg, 0.472 mmol) and the reaction was stirred overnight at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extracts were dried with sodium sulfate, filtered, and concentrated and purified by normal phase chromatography to give the title compound. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.24 (t, J=5.9 Hz, 1H), 8.49 (d, J=7.0 Hz, 1H), 8.35 (s, 1H), 7.89 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.41 (s, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 3.91 (p, J=7.2 Hz, 1H), 3.74 (dd, J=9.8, 7.3 Hz, 1H), 3.51-3.35 (m, 3H), 2.99 (d, J=6.6 Hz, 2H), 2.46-2.33 (m, 1H), 2.24-2.03 (m, 2H), 1.03 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 448 (M+H)+.


Example 752
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(phenylsulfonyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 682, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.20 (t, J=5.9 Hz, 1H), 8.50 (dd, J=7.0, 0.9 Hz, 1H), 8.21 (s, 1H), 7.89 (t, J=0.9 Hz, 1H), 7.84-7.77 (m, 2H), 7.74-7.65 (m, 1H), 7.65-7.57 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (bs, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.47 (d, J=5.9 Hz, 2H), 3.80-3.59 (m, 2H), 3.44-3.31 (m, 3H), 2.32-2.17 (m, 1H), 2.06-1.93 (m, 1H); MS (ESI(+)) m/e 468 (M+H)+.


Example 753
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(2-methylpropyl)sulfonyl]-1,2,3,6-tetrahydropyridin-4-yl}furan-2-carboxamide

The title compound was prepared as described in Example 682, substituting 2-methylpropane sulfonyl chloride for benzenesulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.04-8.96 (m, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.89-7.87 (m, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (s, 1H), 7.13 (d, J=3.5 Hz, 1H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.62-6.57 (m, 1H), 6.56-6.51 (m, 1H), 4.47 (d, J=6.1 Hz, 2H), 3.97-3.91 (m, 2H), 3.40 (t, J=5.7 Hz, 2H), 2.97 (d, J=6.5 Hz, 2H), 2.54-2.48 (m, 2H), 2.19-2.05 (m, 1H), 1.07-1.01 (m, 6H); MS (ESI(+)) m/e 443 (M+H)+.


Example 754
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.10-9.01 (m, 2H), 8.53 (d, J=1.3 Hz, 1H), 8.18-8.16 (m, 1H), 8.14 (d, J=0.5 Hz, 1H), 7.83-7.79 (m, 2H), 7.76 (d, J=3.9 Hz, 1H), 7.22 (d, J=3.9 Hz, 1H), 4.54 (d, J=5.7 Hz, 2H), 3.92 (d, J=7.2 Hz, 2H), 2.13 (dp, J=13.6, 6.7 Hz, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 381 (M+H)+.


Example 755
tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl]-1H-pyrazol-1-yl)methyl}-4-methylpiperidine-1-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.02 (t, J=6.0 Hz, 1H), 8.49 (dd, J=7.0, 0.8 Hz, 1H), 8.13 (s, 1H), 7.91-7.86 (m, 1H), 7.81 (d, J=0.4 Hz, 1H), 7.74 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.23 (d, J=3.8 Hz, 1H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 4.48 (d, J=5.8 Hz, 2H), 4.02 (s, 2H), 3.65-3.50 (m, 2H), 3.19-3.02 (m, 2H), 1.47-1.34 (m, 11H), 1.30-1.15 (m, 2H), 0.93 (s, 3H); MS (ESI(+)) m/e 535 (M+H)+.


Example 789
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate. 1H NMR (500 MHz, DMSO-d6) δ ppm 14.80 (s, 1H), 9.65 (t, J=6.0 Hz, 1H), 9.20 (s, 1H), 8.99 (s, 1H), 8.91 (d, J=7.0 Hz, 1H), 8.36 (d, J=2.0 Hz, 1H), 8.21 (s, 1H), 8.17 (d, J=2.1 Hz, 1H), 7.96 (d, J=3.9 Hz, 1H), 7.86 (s, 1H), 7.84 (s, 1H), 7.51 (dd, J=7.0, 1.4 Hz, 1H), 7.28 (d, J=3.8 Hz, 1H), 4.64 (d, J=5.8 Hz, 2H), 4.10 (s, 2H), 3.19-3.12 (m, 2H), 3.04-2.96 (m, 2H), 1.74-1.59 (m, 2H), 1.57-1.46 (m, 2H), 0.96 (s, 3H); MS (ESI(+)) m/e 435 (M+H)+.


Example 790
5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.97 (t, J=6.1 Hz, 1H), 8.50 (dd, J=13.4, 3.5 Hz, 1H), 8.16 (s, 1H), 7.94 (s, 1H), 7.92 (s, 1H), 7.56 (d, J=1.1 Hz, 1H), 7.43 (s, 1H), 7.18 (d, J=3.5 Hz, 1H), 6.89 (dd, J=7.0, 1.5 Hz, 1H), 6.71 (d, J=6.4 Hz, 1H), 4.51 (d, J=6.1 Hz, 2H), 4.46 (d, J=21.9 Hz, 2H), 3.81-3.70 (m, 2H), 3.56-3.45 (m, 2H), 1.89-1.68 (m, 2H), 1.53 (t, J=11.7 Hz, 2H); MS (ESI(+)) m/e 424 (M+H)+.


Example 801
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(phenylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 682, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (300 MHz, DMSO-d6). δ ppm 8.97 (t, J=6.1 Hz, 1H), 8.47 (d, J=6.5 Hz, 1H), 7.88 (s, 1H), 7.85-7.78 (m, 2H), 7.75-7.68 (m, 1H), 7.69-7.60 (m, 2H), 7.51 (d, J=1.2 Hz, 1H), 7.37 (s, 1H), 7.10 (d, J=3.5 Hz, 1H), 6.82 (dd, J=7.0, 1.7 Hz, 1H), 6.54 (d, J=3.5 Hz, 1H), 6.46-6.43 (m, 1H), 4.46 (d, J=6.1 Hz, 2H), 3.79-3.74 (m, 2H), 3.28-3.21 (m, 2H), 2.45 (s, 2H); MS (ESI(+)) m/e 463 (M+H)+.


Example 802
2-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 52A, substituting 2-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(piperidin-4-yl)thiazole-5-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6). δ ppm 9.23 (t, J=5.9 Hz, 1H), 8.49 (d, J=6.9 Hz, 1H), 8.34 (s, 1H), 7.89 (s, 1H), 7.56-7.36 (m, 4H), 7.35-7.25 (m, 2H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 4.61-4.52 (m, 1H), 4.48 (d, J=5.9 Hz, 2H), 3.51-3.39 (m, 1H), 3.42-3.34 (m, 1H), 3.23 (t, J=12.1 Hz, 1H), 3.01 (td, J=12.7, 2.9 Hz, 1H), 2.21-2.13 (m, 1H), 2.08-1.97 (m, 1H), 1.77-1.54 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 803
5-[1-(2-fluorobenzoyl)-1,2,3,6-tetrahydropyridin-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6). δ ppm 8.66-8.58 (m, 1H), 8.45-8.39 (m, 1H), 7.81 (s, 1H), 7.54-7.44 (m, 2H), 7.43-7.36 (m, 2H), 7.31-7.21 (m, 2H), 7.08 (d, J=3.5 Hz, 1H), 6.82 (dd, J=6.9, 1.7 Hz, 1H), 6.53 (d, J=3.4 Hz, 1H), 6.48 (bs, 1H), 4.47 (d, J=6.1 Hz, 2H), 4.41-3.34 (m, 4H), 2.52-2.37 (m, 2H); MS (ESI(+)) m/e 445 (M+H)+.


Example 804
2-[1-(2-fluorobenzoyl)pyrrolidin-3-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6). δ ppm 8.95-8.88 (m, 1H), 8.43 (d, J=7.0 Hz, 1H), 8.32-8.17 (m, 1H), 7.82 (s, 1H), 7.53-7.35 (m, 4H), 7.30-7.19 (m, 2H), 6.85-6.78 (m, 1H), 4.50-4.44 (m, 2H), 4.05-3.23 (m, 5H), 2.45-2.11 (m, 2H); MS (ESI(+)) m/e 450 (M+H)+.


Example 805
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(2-methylpropanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.28-9.19 (m, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 8.34 (d, J=2.4 Hz, 1H), 7.91-7.87 (m, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.41 (s, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.11-3.33 (m, 5H), 3.17 (d, J=5.2 Hz, 1H), 2.74-2.59 (m, 1H), 2.46-2.00 (m, 6H), 1.03-0.97 (m, 1H); MS (ESI(+)) m/e 398 (M+H)+.


Example 806
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-[1-(3-methylbutanoyl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.28-9.19 (m, 1H), 8.49 (d, J=7.0 Hz, 1H), 8.34 (d, J=2.4 Hz, 1H), 7.91-7.87 (m, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.43-7.38 (m, 1H), 6.83 (dd, J=7.0, 1.7 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 3.97-3.72 (m, 2H), 3.70-3.46 (m, 2H), 3.17 (d, J=5.1 Hz, 1H), 2.45-1.91 (m, 5H), 0.94-0.86 (m, 6H); MS (ESI(+)) m/e 412 (M+H)+.


Example 807
2-(1-benzoylpyrrolidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyridin-7-ylmethyl)-2-(pyrrolidin-3-yl)thiazole-5-carboxamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.94-8.87 (m, 1H), 8.43 (d, J=6.9 Hz, 1H), 8.27 (s, 1H), 8.23-8.16 (m, 1H), 7.82 (s, 1H), 7.52-7.38 (m, 6H), 6.81 (dd, J=6.9, 1.7 Hz, 1H), 4.47 (d, J=5.8 Hz, 2H), 3.94-3.84 (m, 2H), 3.76-3.53 (m, 3H), 2.44-2.34 (m, 1H), 2.24-2.14 (m, 1H); MS (ESI(+)) m/e 432 (M+H)+.


Example 808
tert-butyl 4-[2-(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)ethyl]piperazine-1-carboxylate
Example 808A
tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.500 g, 2.58 mmol), tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (0.593 g, 2.58 mmol) and 2-(tributylphosphoranylidene)acetonitrile (0.746 g, 3.09 mmol) were stirred together in toluene (10 ml) at 85° C. overnight. The reaction was concentrated and purified by normal phase chromatography to give the title compound.


Example 808B
tert-butyl 4-[2-(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)ethyl]piperazine-1-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.02 (t, J=6.0 Hz, 1H), 8.53-8.45 (m, 1H), 8.16 (s, 1H), 7.89 (d, J=0.7 Hz, 1H), 7.79 (d, J=0.5 Hz, 1H), 7.74 (d, J=3.8 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (s, 1H), 7.22 (d, J=3.9 Hz, 1H), 6.84 (dd, J=7.0, 1.6 Hz, 1H), 4.48 (d, J=5.9 Hz, 2H), 4.23 (t, J=6.5 Hz, 2H), 3.29-3.25 (m, 2H), 2.74 (t, J=6.6 Hz, 2H), 2.42-2.33 (m, 4H), 1.38 (s, 9H); MS (ESI(+)) m/e 536 (M+H)+.


Example 809
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-[2-(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl]-1H-pyrazol-1-yl)ethyl}piperazine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.34 (t, J=5.9 Hz, 1H), 8.94 (s, 2H), 8.87 (d, J=7.0 Hz, 1H), 8.33 (dd, J=2.1, 0.7 Hz, 1H), 8.22 (d, J=0.8 Hz, 1H), 8.15 (d, J=2.1 Hz, 1H), 7.87 (d, J=0.8 Hz, 1H), 7.82 (d, J=3.9 Hz, 1H), 7.79 (s, 1H), 7.47 (dd, J=7.0, 1.5 Hz, 1H), 7.27 (d, J=3.8 Hz, 1H), 4.65 (d, J=5.9 Hz, 2H), 4.43-4.34 (m, 2H), 3.22-3.16 (m, 6H), 2.98-2.89 (m, 4H); MS (ESI(+)) m/e 436 (M+H)+.


Example 810
5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide
Example 810A
N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromofuran-2-carboxamide

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 5-bromofuran-2-carboxylic acid for 4-nitrobenzoic acid.


Example 810B
5-{1-[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-fluorotetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromofuran-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.93 (t, J=6.0 Hz, 1H), 8.90-8.85 (m, 1H), 8.48 (s, 1H), 8.13 (s, 1H), 7.92 (d, J=0.5 Hz, 1H), 7.84 (dd, J=9.2, 0.7 Hz, 1H), 7.66 (dd, J=9.2, 1.7 Hz, 1H), 7.16 (d, J=3.6 Hz, 1H), 6.70 (d, J=3.5 Hz, 1H), 4.56 (d, J=6.0 Hz, 2H), 4.45 (d, J=21.8 Hz, 2H), 3.82-3.66 (m, 2H), 3.51 (td, J=11.2, 2.0 Hz, 2H), 1.92-1.63 (m, 2H), 1.60-1.42 (m, 2H); MS (ESI(+)) m/e 425 (M+H)+.


Example 811
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide
Example 811A
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{4-[(imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 811B
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.24 (s, 1H), 8.72-8.68 (m, 1H), 8.27-8.23 (m, 1H), 8.11-8.07 (m, 1H), 7.88-7.82 (m, 2H), 7.41-7.35 (m, 2H), 4.76 (s, 2H), 4.75-4.66 (m, 1H), 4.24-4.15 (m, 1H), 3.29-3.18 (m, 1H), 3.06-2.85 (m, 2H), 2.78-2.64 (m, 1H), 2.02-1.84 (m, 2H), 1.74-1.52 (m, 2H), 1.17-1.07 (m, 6H); MS (ESI(+)) m/e 406 (M+H)+.


Example 812
4-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 4-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.29-9.25 (m, 1H), 8.72 (d, J=1.4 Hz, 1H), 8.27 (d, J=1.7 Hz, 1H), 8.12 (d, J=1.7 Hz, 1H), 7.89-7.83 (m, 2H), 7.55-7.45 (m, 2H), 7.44-7.38 (m, 2H), 7.25-7.16 (m, 2H), 4.87-4.84 (m, 1H), 4.77 (s, 2H), 3.90-3.79 (m, 1H), 3.33-3.19 (m, 1H), 3.03-2.89 (m, 2H), 2.07-1.61 (m, 4H); MS (ESI(+)) m/e 458 (M+H)+.


Example 813
4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 2,5-difluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.23 (s, 1H), 8.69 (s, 1H), 8.24 (d, J=1.6 Hz, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.89-7.83 (m, 2H), 7.43-7.36 (m, 2H), 7.31-7.15 (m, 3H), 4.84-4.73 (m, 3H), 3.71-3.62 (m, 1H), 3.36-3.24 (m, 1H), 3.04-2.90 (m, 2H), 2.04-1.95 (m, 1H), 1.92-1.61 (m, 3H); MS (ESI(+)) m/e 476 (M+H)+.


Example 814
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 1-methylcyclopropanecarboxylic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.28 (s, 1H), 8.73 (s, 1H), 8.28 (d, J=1.7 Hz, 1H), 8.13 (d, J=1.7 Hz, 1H), 7.89-7.83 (m, 2H), 7.42-7.36 (m, 2H), 4.78 (s, 2H), 4.62-4.53 (m, 2H), 3.20-2.70 (m, 3H), 1.97-1.89 (m, 2H), 1.72-1.57 (m, 2H), 1.33 (s, 3H), 0.96-0.89 (m, 2H), 0.71-0.58 (m, 2H); MS (ESI(+)) m/e 418 (M+H)+.


Example 815
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 3,3,3-trifluoropropanoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 9.22 (d, J=1.4 Hz, 1H), 8.68 (d, J=1.4 Hz, 1H), 8.23 (d, J=1.9 Hz, 1H), 8.06 (d, J=1.6 Hz, 1H), 7.89-7.82 (m, 2H), 7.42-7.34 (m, 2H), 4.81-4.65 (m, 3H), 4.11-3.99 (m, 1H), 3.62-3.44 (m, 2H), 3.37-3.21 (m, 1H), 3.01-2.86 (m, 1H), 2.85-2.71 (m, 1H), 1.99-1.85 (m, 2H), 1.85-1.54 (m, 2H); MS (ESI(+)) m/e 446 (M+H)+.


Example 816
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3-methylbutanoyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (500 MHz, methanol-d4) δ ppm 99.24 (d, J=1.4 Hz, 1H), 8.70 (d, J=1.4 Hz, 1H), 8.25 (d, J=1.7 Hz, 1H), 8.09 (d, J=1.7 Hz, 1H), 7.89-7.82 (m, 2H), 7.41-7.34 (m, 2H), 4.79-4.66 (m, 3H), 4.19-4.07 (m, 1H), 3.30-3.16 (m, 1H), 3.00-2.85 (m, 1H), 2.80-2.63 (m, 1H), 2.36-2.29 (m, 2H), 2.17-2.00 (m, 1H), 2.01-1.84 (m, 2H), 1.75-1.50 (m, 2H), 0.99 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 420 (M+H)+.


Example 817
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(propan-2-ylsulfonyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 682, substituting propane-2-sulfonyl chloride for benzenesulfonyl chloride and N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (500 MHz, methanol-d4) δ ppm 9.21 (d, J=1.4 Hz, 1H), 8.67 (d, J=1.4 Hz, 1H), 8.22 (d, J=1.6 Hz, 1H), 8.05 (d, J=1.6 Hz, 1H), 7.89-7.82 (m, 2H), 7.40-7.35 (m, 2H), 4.85-4.79 (m, 1H), 4.75 (s, 2H), 3.96-3.85 (m, 2H), 3.12-3.00 (m, 2H), 2.88-2.74 (m, 1H), 1.95-1.85 (m, 2H), 1.84-1.65 (m, 2H), 1.33 (d, J=6.8 Hz, 6H); MS (ESI(+)) m/e 442 (M+H)+.


Example 818
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-isobutyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=6.1 Hz, 1H), 8.49 (dd, J=7.0, 0.7 Hz, 1H), 7.89 (s, 1H), 7.54-7.51 (m, 2H), 7.41 (s, 1H), 7.30 (d, J=3.6 Hz, 1H), 6.96 (d, J=3.6 Hz, 1H), 6.85 (dd, J=7.0, 1.6 Hz, 1H), 6.76 (d, J=1.9 Hz, 1H), 4.50 (d, J=6.0 Hz, 2H), 4.22 (d, J=7.3 Hz, 2H), 2.04 (dp, J=13.8, 6.8 Hz, 1H), 0.81 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 364 (M+H)+.


Example 819
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide
Example 819A
5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid

The title compound was prepared as described in Example 51A, substituting 5-bromofuran-2-carboxylic acid for 4-bromoaniline.


Example 819B
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.05-9.02 (m, 1H), 8.90 (t, J=6.0 Hz, 1H), 8.52 (d, J=1.4 Hz, 1H), 8.19-8.14 (m, 2H), 7.90-7.88 (m, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.17 (d, J=3.5 Hz, 1H), 6.65 (d, J=3.5 Hz, 1H), 4.56 (d, J=5.9 Hz, 2H), 3.96 (d, J=7.1 Hz, 2H), 2.20-2.07 (m, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 365 (M+H)+.


Example 820
5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 8.94-8.85 (m, 2H), 8.48 (s, 1H), 8.14 (s, 1H), 7.87 (s, 1H), 7.84 (d, J=9.1 Hz, 1H), 7.66 (dd, J=9.1, 1.7 Hz, 1H), 7.16 (d, J=3.5 Hz, 1H), 6.64 (d, J=3.5 Hz, 1H), 4.56 (d, J=6.0 Hz, 2H), 3.95 (d, J=7.1 Hz, 2H), 2.21-1.97 (m, 1H), 0.90-0.76 (m, 6H); MS (ESI(+)) m/e 365 (M+H)+.


Example 821
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(3-methylbutyl)-1H-pyrazol-5-yl]furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-isopentyl-1H-pyrazol-5-ylboronic acid for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.03 (t, J=6.1 Hz, 1H), 8.49 (dd, J=7.0, 0.8 Hz, 1H), 7.89 (s, 1H), 7.58-7.43 (m, 2H), 7.43-7.37 (m, 1H), 7.30 (d, J=3.5 Hz, 1H), 6.95 (d, J=3.6 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.73 (d, J=1.9 Hz, 1H), 4.50 (d, J=6.0 Hz, 2H), 4.44-4.36 (m, 2H), 1.68-1.38 (m, 3H), 0.84 (d, J=6.4 Hz, 6H); MS (ESI(+)) m/e 378 (M+H)+.


Example 822
5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-bromofuran-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.95-8.83 (m, 2H), 8.48 (s, 1H), 8.15-8.09 (m, 1H), 7.88 (d, J=0.4 Hz, 1H), 7.83 (dd, J=9.2, 0.7 Hz, 1H), 7.66 (dd, J=9.2, 1.7 Hz, 1H), 7.16 (d, J=3.5 Hz, 1H), 6.66 (d, J=3.5 Hz, 1H), 4.56 (d, J=6.0 Hz, 2H), 4.06 (s, 2H), 3.68 (dt, J=11.4, 4.5 Hz, 2H), 3.51 (ddd, J=11.9, 9.3, 2.9 Hz, 2H), 1.50 (ddd, J=13.4, 9.2, 4.2 Hz, 2H), 1.31-1.17 (m, 2H), 0.96 (s, 3H); MS (ESI(+)) m/e 421 (M+H)+.


Example 823
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide
Example 823A
Methyl 5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophene-2-carboxylate

The title compound was prepared as described in Example 688D, substituting 5-(methoxycarbonyl)thiophene-2-carboxylic acid for lithium 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate.


Example 823B
Lithium 5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophene-2-carboxylate

The title compound was prepared as described in Example 688C, substituting methyl 5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophene-2-carboxylate for ethyl 2-(1-phenylpiperidin-4-yl)thiazole-5-carboxylate.


Example 823C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting), (R)-2-(methoxymethyl)pyrrolidine for 3-methylbutan-1-amine and lithium 5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophene-2-carboxylate for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.23 (t, J=6.0 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.90-7.88 (m, 1H), 7.79 (d, J=4.0 Hz, 1H), 7.60 (d, J=4.0 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.42-7.39 (m, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.35-4.23 (m, 1H), 3.78-3.65 (m, 2H), 3.26 (s, 3H), 2.02-1.81 (m, 4H); MS (ESI(+)) m/e 399 (M+H)+.


Example 824
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting), 2-isobutylpyrrolidine for 3-methylbutan-1-amine and lithium 5-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)thiophene-2-carboxylate for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6). δ ppm 9.23 (t, J=6.0 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.90-7.88 (m, 1H), 7.79 (d, J=4.0 Hz, 1H), 7.60 (d, J=4.0 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.42-7.39 (m, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 4.49 (d, J=5.9 Hz, 2H), 4.35-4.23 (m, 1H), 3.78-3.65 (m, 2H), 3.26 (s, 3H), 2.02-1.81 (m, 4H); MS (ESI(+)) m/e 411 (M+H)+.


Example 825
5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-neopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.89 (t, J=6.1 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 8.11 (d, J=0.5 Hz, 1H), 7.95-7.83 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.46-7.34 (m, 1H), 7.17 (d, J=3.4 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.66 (d, J=3.5 Hz, 1H), 4.49 (d, J=6.0 Hz, 2H), 3.95 (s, 2H), 0.92 (s, 9H); MS (ESI(+)) m/e 378 (M+H)+.


Example 826
4-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.08-9.00 (m, 2H), 8.49 (d, J=1.4 Hz, 1H), 8.16-8.13 (m, 1H), 7.92-7.85 (m, 2H), 7.79 (d, J=1.0 Hz, 1H), 7.57-7.23 (m, 6H), 4.74-4.61 (m, 1H), 4.57 (d, J=5.7 Hz, 2H), 3.54-3.43 (m, 1H), 3.24-3.14 (m, 1H), 3.00-2.79 (m, 2H), 1.97-1.84 (m, 1H), 1.82-1.47 (m, 3H); MS (ESI(+)) m/e 458 (M+H)+.


Example 827
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide
Example 827A
tert-butyl 4-(5-(ethoxycarbonyl)thiophen-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and ethyl 5-bromothiophene-2-carboxylate for 4-bromoaniline.


Example 827B
tert-butyl 4-(5-(ethoxycarbonyl)thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(5-(ethoxycarbonyl)thiophen-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 827C
5-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiophene-2-carboxylic acid

In a 250 mL round bottom flask was mixed tert-butyl 4-(5-(ethoxycarbonyl)thiophen-2-yl)piperidine-1-carboxylate (5.00 g, 14.73 mmol) in tetrahydrofuran (50 ml). Aqueous 4N NaOH (38.41 ml, 73.6 mmol) solution was added along with some methanol (10 ml) to get a single phase solution. The mixture was stirred overnight at room temperature. The solvents were removed to give a white slurry that was diluted with water and adjusted to pH of 5 with 1N aqueous hydrochloric acid. Filtration provided the title compound.


Example 827D
tert-butyl 4-(5-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 827E
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)thiophen-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 827F
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (m, 2H), 8.50 (d, J=1.5 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.7 Hz, 1H), 7.50 (m, 1H), 7.43 (m, 1H), 7.31 (m, 2H), 6.98 (d, J=3.8 Hz, 1H), 4.60 (m, 1H), 4.52 (d, J=5.8 Hz, 2H), 3.45 (m, 1H), 3.18 (m, 2H), 2.93 (m, 1H), 2.12-1.85 (m, 2H), 1.52 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 828
5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 4-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (m, 2H), 8.51 (d, J=1.4 Hz, 1H), 8.16 (t, J=0.8 Hz, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.70 (d, J=3.8 Hz, 1H), 7.49 (m, 2H), 7.28 (m, 2H), 6.99 (dd, J=3.7, 0.8 Hz, 1H), 4.54 (m, 1H), 4.52 (d, J=5.8 Hz, 2H), 3.65 (m, 1H), 3.15 (m, 2H), 2.93 (m, 1H), 1.97 (m, 2H), 1.59 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 829
5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2,4-difluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (m, 2H), 8.50 (d, J=1.4 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 7.52 (m, 1H), 7.37 (td, J=9.7, 2.4 Hz, 1H), 7.19 (td, J=8.5, 2.5 Hz, 1H), 6.98 (d, J=3.8 Hz, 1H), 4.58 (m, 1H), 4.52 (d, J=5.8 Hz, 2H), 3.43 (m, 1H), 3.17 (m, 2H), 2.92 (m, 1H), 2.00 (m, 2H), 1.52 (m, 2H); MS (ESI(+)) m/e 482 (M+H)+.


Example 830
5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2,5-difluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.04 (m, 2H), 8.51 (d, J=1.5 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J=1.1 Hz, 1H), 7.70 (d, J=3.8 Hz, 1H), 7.56 (m, 1H), 7.36 (m, 2H), 6.98 (d, J=3.8 Hz, 1H), 4.57 (m, 1H), 4.52 (d, J=5.8 Hz, 2H), 3.46 (m, 1H), 3.17 (m, 2H), 2.93 (m, 1H), 2.02 (m, 2H), 1.55 (m, 2H); MS (ESI(+)) m/e 482 (M+H)+.


Example 831
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide
Example 831A
tert-butyl 4-(5-(([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)carbamoyl)thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 831B
N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(5-(([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)carbamoyl)thiophen-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 831C
5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 7.50 (m, 1H), 7.42 (m, 1H), 7.31 (m, 2H), 6.97 (dd, J=3.7, 0.8 Hz, 1H), 4.60 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.45 (m, 1H), 3.17 (m, 2H), 2.93 (m, 1H), 2.07 (m, 1H), 1.93 (m, 1H), 1.54 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 832
5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 3-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.66 (m, 2H), 7.50 (m, 1H), 7.34-7.22 (m, 3H), 6.98 (d, J=3.8 Hz, 1H), 4.55 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.56 (m, 1H), 3.13 (m, 2H), 2.91 (m, 1H), 1.97 (m, 2H), 1.60 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 833
5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 4-fluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 7.47 (m, 2H), 7.27 (m, 2H), 6.98 (dd, J=3.7, 0.8 Hz, 1H), 4.55 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.62 (m, 1H), 3.14 (m, 2H), 2.91 (m, 1H), 1.97 (m, 2H), 1.58 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 834
5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2,4-difluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.9 Hz, 1H), 8.86 (m, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 7.52 (m, 1H), 7.36 (td, J=9.7, 2.4 Hz, 1H), 7.19 (m, 1H), 6.97 (dd, J=3.8, 0.8 Hz, 1H), 4.57 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.46 (m, 1H), 3.18 (m, 2H), 2.92 (m, 1H), 2.07 (m, 1H), 1.93 (m, 1H), 1.52 (m, 2H); MS (ESI(+)) m/e 482 (M+H)+.


Example 835
5-[1-(2,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 2,5-difluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 7.37 (m, 3H), 6.97 (dd, J=3.7, 0.8 Hz, 1H), 4.57 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.46 (m, 1H), 3.19 (m, 2H), 2.93 (m, 1H), 2.13 (m, 1H), 1.92 (m, 1H), 1.54 (m, 2H); MS (ESI(+)) m/e 482 (M+H)+.


Example 836
5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 52A, substituting 3,5-difluorobenzoyl chloride for 2-cyclopentylacetyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 7.34 (tt, J=9.4, 2.4 Hz, 1H), 7.19 (m, 2H), 6.98 (dd, J=3.8, 0.8 Hz, 1H), 4.55 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.55 (m, 1H), 3.15 (m, 2H), 2.90 (m, 1H), 2.03 (m, 1H), 1.90 (m, 1H), 1.61 (m, 2H); MS (ESI(+)) m/e 482 (M+H)+.


Example 837
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(2-methylpropanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (m, 2H), 8.50 (d, J=1.4 Hz, 1H), 8.16 (m, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.49 (m, 1H), 4.02 (m, 1H), 3.13 (m, 2H), 2.90 (m, 1H), 2.64 (m, 1H), 1.99 (m, 2H), 1.43 (m, 2H), 1.00 (m, 6H); MS (ESI(+)) m/e 412 (M+H)+.


Example 838
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(3-methylbutanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (m, 2H), 8.50 (d, J=1.4 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.49 (m, 1H), 3.96 (m, 1H), 3.10 (m, 2H), 2.64 (m, 1H), 2.21 (d, J=7.0 Hz, 2H), 1.99 (m, 3H), 1.43 (m, 2H), 0.90 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 426 (M+H)+.


Example 839
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (1-methylcyclopropyl)carboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (m, 2H), 8.50 (d, J=1.4 Hz, 1H), 8.16 (d, J=0.9 Hz, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 6.97 (dd, J=3.7, 0.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.33 (m, 2H), 3.11 (m, 1H), 2.93 (m, 2H), 1.99 (m, 2H), 1.47 (m, 2H), 1.23 (s, 3H), 0.80 (m, 2H), 0.54 (m, 2H); MS (ESI(+)) m/e 424 (M+H)+.


Example 840
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 4,4,4-trifluorobutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (m, 2H), 8.50 (d, J=1.4 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.47 (m, 1H), 3.94 (m, 1H), 3.13 (m, 2H), 2.66 (m, 3H), 2.50 (m, 2H), 1.97 (m, 2H), 1.57 (m, 1H), 1.41 (m, 1H); MS (ESI(+)) m/e 466 (M+H)+.


Example 841
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and tetrahydro-2H-pyran-4-ylcarboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (m, 2H), 8.50 (d, J=1.4 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.69 (d, J=3.8 Hz, 1H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.47 (m, 1H), 4.07 (m, 1H), 3.84 (m, 2H), 3.40 (m, 2H), 3.13 (m, 2H), 2.89 (m, 1H), 2.64 (m, 1H), 1.98 (m, 2H), 1.77-1.30 (m, 6H); MS (ESI(+)) m/e 454 (M+H)+.


Example 842
5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.9 Hz, 1H), 8.86 (s, 1H), 8.47 (s, 1H), 7.83 (d, J=9.1 Hz, 1H), 7.64 (m, 2H), 6.96 (d, J=3.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.47 (m, 1H), 4.02 (m, 1H), 3.12 (m, 2H), 2.88 (m, 1H), 2.63 (m, 1H), 1.99 (m, 2H), 1.43 (m, 2H), 1.00 (m, 6H); MS (ESI(+)) m/e 412 (M+H)+.


Example 843
5-[1-(3-methylbutanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.47 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.95 (dd, J=3.7, 0.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.48 (m, 1H), 3.96 (m, 1H), 3.10 (m, 2H), 2.63 (m, 1H), 2.21 (m, 2H), 1.98 (m, 3H), 1.43 (m, 2H), 0.90 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 426 (M+H)+.


Example 844
5-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (2S)-2-methylbutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.47 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.95 (d, J=3.8 Hz, 1H), 4.52 (d, J=5.8 Hz, 2H), 4.49 (m, 1H), 4.05 (m, 1H), 3.13 (m, 2H), 2.69 (m, 2H), 1.99 (m, 2H), 1.61-1.18 (m, 4H), 0.98 (m, 3H), 0.82 (m, 3H); MS (ESI(+)) m/e 426 (M+H)+.


Example 845
5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (1-methylcyclopropyl)carboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.9 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.47 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.96 (dd, J=3.7, 0.9 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 4.33 (m, 2H), 3.10 (m, 1H), 2.92 (m, 2H), 1.98 (m, 2H), 1.47 (m, 2H), 1.23 (s, 3H), 0.80 (m, 2H), 0.53 (m, 2H); MS (ESI(+)) m/e 424 (M+H)+.


Example 846
N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 3,3,3-trifluoropropanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.9 Hz, 1H), 8.86 (m, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.65 (m, 2H), 6.95 (dd, J=3.7, 0.9 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 4.45 (m, 1H), 3.90 (m, 1H), 3.66 (m, 2H), 3.13 (m, 2H), 2.70 (m, 1H), 1.97 (m, 2H), 1.57 (m, 1H), 1.42 (m, 1H); MS (ESI(+)) m/e 452 (M+H)+.


Example 847
N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 4,4,4-trifluorobutanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.8 Hz, 1H), 8.86 (m, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.95 (dd, J=3.7, 0.8 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 4.47 (m, 1H), 3.94 (m, 1H), 3.12 (m, 2H), 2.65 (m, 3H), 2.50 (m, 2H), 1.96 (m, 2H), 1.57 (m, 1H), 1.41 (m, 1H); MS (ESI(+)) m/e 466 (M+H)+.


Example 848
5-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (4,4-difluorocyclohexyl)carboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.8 Hz, 1H), 8.86 (m, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 4.48 (m, 1H), 4.06 (m, 1H), 3.13 (m, 2H), 2.82 (m, 1H), 2.65 (m, 1H), 2.10-1.80 (m, 6H), 1.80-1.30 (m, 6H); MS (ESI(+)) m/e 488 (M+H)+.


Example 849
5-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and tetrahydro-2H-pyran-4-ylcarboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.9 Hz, 1H), 8.86 (m, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.95 (dd, J=3.7, 0.8 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 4.48 (m, 1H), 4.06 (m, 1H), 3.84 (m, 2H), 3.38 (m, 2H), 3.12 (m, 2H), 2.89 (m, 1H), 2.64 (m, 1H), 1.98 (m, 2H), 1.65-1.30 (m, 6H); MS (ESI(+)) m/e 454 (M+H)+.


Example 850
5-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 2-hydroxy-2-methylpropanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.8 Hz, 1H), 8.86 (m, 1H), 8.47 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.95 (dd, J=3.7, 0.8 Hz, 1H), 5.39 (s, 1H), 5.00-4.30 (m, 2H), 4.53 (d, J=5.8 Hz, 2H), 3.10 (m, 1H), 3.10-2.60 (m, 2H), 1.96 (m, 2H), 1.50 (m, 2H), 1.32 (s, 6H); MS (ESI(+)) m/e 428 (M+H)+.


Example 851
5-{1-[(1-methylpiperidin-4-yl)carbonyl]piperidin-4-yl}-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and (1-methylpiperidin-4-yl)carboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.8 Hz, 1H), 8.85 (s, 1H), 8.47 (s, 1H), 7.83 (d, J=9.1 Hz, 1H), 7.64 (m, 2H), 6.95 (d, J=3.8 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 4.48 (m, 1H), 4.00 (m, 1H), 3.04 (m, 4H), 2.80-2.57 (m, 4H), 2.13 (s, 3H), 2.07-1.80 (m, 4H), 1.81-0.93 (m, 4H); MS (ESI(+)) m/e 467 (M+H)+.


Example 852
5-[1-(2-cyanobenzoyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and 2-cyanobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (t, J=5.8 Hz, 1H), 8.86 (m, 1H), 8.47 (s, 1H), 7.95 (m, 1H), 7.82 (m, 2H), 7.70-7.57 (m, 4H), 6.96 (dd, J=3.7, 0.8 Hz, 1H), 4.61 (m, 1H), 4.52 (d, J=5.8 Hz, 2H), 3.35 (m, 1H), 3.14 (m, 2H), 2.97 (m, 1H), 2.09 (m, 1H), 1.89 (m, 1H), 1.60 (m, 2H); MS (ESI(+)) m/e 471 (M+H)+.


Example 853
5-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for 3-methylbutan-1-amine and pyridin-2-ylcarboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.8 Hz, 1H), 8.86 (m, 1H), 8.59 (m, 1H), 8.48 (s, 1H), 7.92 (td, J=7.7, 1.7 Hz, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 7.57 (dt, J=7.7, 1.1 Hz, 1H), 7.47 (m, 1H), 6.97 (dd, J=3.7, 0.8 Hz, 1H), 4.58 (m, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.72 (m, 1H), 3.17 (m, 2H), 2.93 (m, 1H), 2.08 (m, 1H), 1.91 (m, 1H), 1.58 (m, 2H); MS (ESI(+)) m/e 447 (M+H)+.


Example 854
2-cyclopentyl-N-{4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}acetamide

The title compound was prepared as described in Example 1A, substituting N-(4-aminophenyl)-2-cyclopentylacetamide for 3-methylbutan-1-amine and 2-(imidazo[1,2-a]pyridin-6-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.12 (bs, 1H), 9.77 (bs, 1H), 8.47-8.44 (m, 1H), 7.94 (s, 1H), 7.58-7.43 (m, 6H), 7.19 (dd, J=9.2, 1.7 Hz, 1H), 3.64 (bs, 2H), 2.30-2.19 (m, 3H), 1.82-1.65 (m, 2H), 1.66-1.43 (m, 4H), 1.26-1.08 (m, 2H); MS (ESI(+)) m/e 377 (M+H)+.


Example 855
tert-butyl 4-{4-[(imidazo[1,2-b]pyridazin-6-ylmethyl)carbamoyl]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-b]pyridazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.15 (t, J=5.9 Hz, 1H), 8.24 (s, 1H), 8.07 (d, J=9.3 Hz, 1H), 7.88-7.82 (m, 2H), 7.75 (d, J=1.2 Hz, 1H), 7.41-7.34 (m, 2H), 7.20 (d, J=9.3 Hz, 1H), 4.63 (d, J=5.8 Hz, 2H), 4.13-4.03 (m, 2H), 2.91-2.67 (m, 3H), 1.80-1.72 (m, 2H), 1.61-1.44 (m, 2H), 1.42 (s, 9H); MS (ESI(+)) m/e 436 (M+H)+.


Example 856
4-[(cyclopentylacetyl)amino]-N-(imidazo[1,2-b]pyridazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-b]pyridazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.38 (d, J=1.9 Hz, 1H), 8.28 (dd, J=9.4, 0.7 Hz, 1H), 8.07 (d, J=1.9 Hz, 1H), 7.90-7.84 (m, 2H), 7.79-7.66 (m, 3H), 4.91-4.79 (m, 2H), 2.43-2.25 (m, 3H), 1.92-1.78 (m, 2H), 1.79-1.50 (m, 4H), 1.33-1.18 (m, 2H); MS (ESI(+)) m/e 378 (M+H)+.


Example 857A
methyl 5-(3-cyclopropylpropioloyl)thiophene-2-carboxylate

Methyl 5-(chlorocarbonyl)thiophene-2-carboxylate (500 mg, 2.443 mmol) was dissolved in triethylamine (5 mL) and the suspension was degassed with nitrogen. Copper(I) iodide (40 mg, 0.210 mmol) and bistriphenylphosphine palladium chloride (40 mg, 0.057 mmol) were added followed by ethynylcyclopropane (162 mg, 2.443 mmol). The mixture was stirred overnight, diluted with methanol and concentrated to dryness. The crude material was partitioned between dichloromethane and water. The organic extracts were dried with sodium sulfate, filtered, concentrated and purified by normal phase chromatography to afford the title compound.


Example 857B
methyl 5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)thiophene-2-carboxylate

Methyl 5-(3-cyclopropylpropioloyl)thiophene-2-carboxylate (100 mg, 0.427 mmol) was dissolved in N,N-dimethylformamide (2 mL), and the solution was cooled to 0° C. Benzylhydrazine hydrochloride (74.5 mg, 0.470 mmol) was added followed by potassium carbonate (77 mg, 0.555 mmol). The mixture was stirred at 0° C. until the ice bath melted and was stirred overnight at room temperature. The solution was partitioned between water and ethyl acetate. The organic extract was dried with sodium sulfate, filtered, concentrated and purified by normal phase chromatography to afford the title compound.


Example 857C
5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 4B, substituting methyl 5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)thiophene-2-carboxylate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 857D
5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 5-(1-benzyl-3-cyclopropyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04 (t, J=5.9 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 7.91-7.87 (m, 1H), 7.74 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.42-7.24 (m, 5H), 7.23-7.15 (m, 2H), 6.84 (dd, J=7.0, 1.7 Hz, 1H), 6.38 (s, 1H), 5.44 (bs, 2H), 4.47 (d, J=5.9 Hz, 2H), 1.94-1.81 (m, 1H), 0.97-0.86 (m, 2H), 0.72-0.59 (m, 2H); MS (ESI(+)) m/e 454 (M+H)+.


Example 858
5-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide
Example 858A
5-bromo-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 5-bromothiophene-2-carboxylic acid for 4-nitrobenzoic acid.


Example 858B

The title compound was prepared as described in Example 51A, substituting 1-neopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.10-8.99 (m, 2H), 8.53 (d, J=1.3 Hz, 1H), 8.17 (d, J=0.9 Hz, 1H), 8.10 (d, J=0.5 Hz, 1H), 7.82-7.78 (m, 2H), 7.76 (d, J=3.8 Hz, 1H), 7.23 (d, J=3.9 Hz, 1H), 4.54 (d, J=5.7 Hz, 2H), 3.92 (s, 2H), 0.92 (s, 9H); MS (ESI(+)) m/e 395 (M+H)+.


Example 859
5-[1-(propan-2-ylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 682, substituting propane-2-sulfonyl chloride for benzenesulfonyl chloride and N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (t, J=5.8 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H), 8.48 (s, 1H), 7.83 (dd, J=9.1, 0.9 Hz, 1H), 7.64 (m, 2H), 6.97 (dd, J=3.7, 0.9 Hz, 1H), 4.53 (d, J=5.8 Hz, 2H), 3.71 (m, 2H), 3.25 (m, 1H), 3.02 (m, 3H), 2.00 (m, 2H), 1.56 (m, 2H), 1.22 (d, J=6.8 Hz, 6H); MS (ESI(+)) m/e 448 (M+H)+.


Example 860
5-[1-(phenylsulfonyl)piperidin-4-yl]-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 682, substituting N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)-5-(piperidin-4-yl)thiophene-2-carboxamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=5.9 Hz, 1H), 8.85 (s, 1H), 8.47 (s, 1H), 7.83 (d, J=9.1 Hz, 1H), 7.81-7.69 (m, 3H), 7.71-7.55 (m, 4H), 6.90 (d, J=3.8 Hz, 1H), 4.51 (d, J=5.8 Hz, 2H), 3.73 (m, 2H), 2.84 (m, 1H), 2.37 (m, 2H), 1.99 (m, 2H), 1.61 (m, 2H); MS (ESI(+)) m/e 482 (M+H)+.


Example 861
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 14(4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.09-9.01 (m, 2H), 8.53 (d, J=1.4 Hz, 1H), 8.18-8.15 (m, 1H), 8.13 (d, J=0.5 Hz, 1H), 7.83-7.79 (m, 2H), 7.76 (d, J=3.9 Hz, 1H), 7.23 (d, J=3.9 Hz, 1H), 4.54 (d, J=5.7 Hz, 2H), 4.04 (s, 2H), 3.68 (dt, J=11.4, 4.5 Hz, 2H), 3.51 (ddd, J=11.8, 9.2, 2.9 Hz, 2H), 1.50 (ddd, J=13.4, 9.1, 4.1 Hz, 2H), 1.33-1.18 (m, 2H), 0.96 (s, 3H); MS (ESI(+)) m/e 437 (M+H)+.


Example 862
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 3-methylbutan-1-amine and 2-(imidazo[1,2-a]pyridin-6-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.14 (s, 1H), 8.52 (s, 1H), 8.01 (d, J=1.3 Hz, 1H), 7.65-7.58 (m, 2H), 7.54-7.47 (m, 2H), 7.31 (dd, J=9.2, 1.7 Hz, 1H), 7.20-7.13 (m, 2H), 4.11-3.99 (m, 2H), 3.68 (s, 2H), 2.89-2.54 (m, 3H), 1.76-1.66 (m, 2H), 1.53-1.32 (m, 11H); MS (ESI(+)) m/e 435 (M+H)+.


Example 863
N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide
Example 863A
2-(imidazo[1,2-a]pyridin-6-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-6-ylacetyl)amino]phenyl}piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 863B
N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide

The title compound was prepared as described in Example 1A, substituting 2-(imidazo[1,2-a]pyridin-6-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.77 (s, 1H), 8.21 (d, J=2.2 Hz, 1H), 8.03 (d, J=2.1 Hz, 1H), 8.01-7.94 (m, 1H), 7.93-7.87 (m, 1H), 7.55-7.35 (m, 4H), 7.33-7.26 (m, 1H), 7.25-7.17 (m, 3H), 4.83-4.74 (m, 1H), 3.91 (s, 2H), 3.68-3.58 (m, 1H), 3.30-3.18 (m, 1H), 3.02-2.78 (m, 2H), 2.01-1.91 (m, 1H), 1.87-1.50 (m, 3H); MS (ESI(+)) m/e 457 (M+H)+.


Example 864
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(phenylsulfonyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 682, substituting N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)benzamide. 1H NMR (400 MHz, methanol-d4) δ ppm 9.04-8.96 (m, 1H), 8.51 (s, 1H), 8.05 (s, 1H), 7.85-7.79 (m, 5H), 7.73-7.66 (m, 1H), 7.67-7.59 (m, 2H), 7.35-7.28 (m, 2H), 4.72-4.67 (m, 2H), 3.96-3.88 (m, 2H), 2.63-2.51 (m, 1H), 2.48-2.37 (m, 2H), 1.93-1.85 (m, 2H), 1.86-1.72 (m, 2H); MS (ESI(+)) m/e 476 (M+H)+.


Example 865
2-(imidazo[1,2-a]pyridin-6-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}acetamide

The title compound was prepared as described in Example 1A, substituting 2-(imidazo[1,2-a]pyridin-6-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.77 (d, J=1.4 Hz, 1H), 8.21 (dd, J=2.2, 0.7 Hz, 1H), 8.03 (d, J=2.2 Hz, 1H), 8.01-7.94 (m, 1H), 7.93-7.87 (m, 1H), 7.53-7.47 (m, 2H), 7.23-7.17 (m, 2H), 4.73-4.64 (m, 1H), 4.21-4.13 (m, 1H), 3.91 (s, 2H), 3.27-3.14 (m, 1H), 2.99 (kept, J=6.7 Hz, 1H), 2.88-2.74 (m, 1H), 2.76-2.63 (m, 1H), 1.96-1.81 (m, 2H), 1.71-1.45 (m, 2H), 1.16-1.07 (m, 6H); MS (ESI(+)) m/e 405 (M+H)+.


Example 866
N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-6-yl)acetamide

The title compound was prepared as described in Example 1A, substituting 2-(imidazo[1,2-a]pyridin-6-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and 2,4-difluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.77 (d, J=1.4 Hz, 1H), 8.23-8.18 (m, 1H), 8.03 (d, J=2.2 Hz, 1H), 8.01-7.94 (m, 1H), 7.93-7.87 (m, 1H), 7.54-7.42 (m, 3H), 7.25-7.19 (m, 2H), 7.13-7.05 (m, 2H), 4.84-4.74 (m, 2H), 3.91 (s, 2H), 3.68-3.59 (m, 1H), 3.30-3.20 (m, 1H), 3.02-2.79 (m, 1H), 2.00-1.91 (m, 1H), 1.88-1.52 (m, 3H); MS (ESI(+)) m/e 475 (M+H)+.


Example 877
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}benzamide
Example 877A
methyl 4-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)benzoate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(methoxycarbonyl)benzoic acid for 4-nitrobenzoic acid.


Example 877B
4-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)benzoic acid

The title compound was prepared as described in Example 4B, substituting methyl 4-((imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl)benzoate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 877C
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(2-methylpropyl)pyrrolidin-1-yl]carbonyl}benzamide

The title compound was prepared as described in Example 1A, substituting 2-isobutylpyrrolidine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.17 (t, J=5.9 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.95 (d, J=8.2 Hz, 2H), 7.89 (d, J=1.2 Hz, 1H), 7.56 (d, J=8.0 Hz, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 6.86 (dd, J=7.0, 1.7 Hz, 1H), 4.52 (d, J=5.9 Hz, 2H), 4.25-4.14 (m, 1H), 3.58-3.51 (m, 1H), 3.51-3.38 (m, 1H), 2.09-1.53 (m, 5H), 1.33-1.17 (m, 2H), 0.94 (d, J=6.4 Hz, 6H); MS (ESI(+)) m/e 405 (M+H)+.


Example 878
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}benzamide

The title compound was prepared as described in Example 1A, substituting (2R)-2-(methoxymethyl)pyrrolidine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.18 (t, J=4.8 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 7.95 (d, J=8.3 Hz, 2H), 7.88 (s, 1H), 7.57 (d, J=7.7 Hz, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 6.86 (dd, J=7.0, 1.6 Hz, 1H), 4.52 (d, J=5.9 Hz, 2H), 3.62-2.88 (br m, 8H), 2.05-1.64 (br m, 4H); MS (ESI(+)) m/e 393 (M+H)+.


Example 881
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(phenylsulfonyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-7-ylmethanamine for 3-methylbutan-1-amine and 4-(phenylsulfonyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.53 (t, J=5.9 Hz, 1H), 8.83 (d, J=6.9 Hz, 1H), 8.30 (d, J=2.1 Hz, 1H), 8.16-8.07 (m, 5H), 8.03-7.97 (m, 2H), 7.80-7.61 (m, 4H), 7.46 (dd, J=6.9, 1.6 Hz, 1H), 4.68 (d, J=5.8 Hz, 2H); MS (ESI(+)) m/e 392 (M+H)+.


Example 882
4-(phenylsulfonyl)-N-([1,2,4]triazolo[1,5-a]pyridin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting [1,2,4]triazolo[1,5-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(phenylsulfonyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.32 (t, J=5.8 Hz, 1H), 8.92-8.87 (m, 1H), 8.49-8.46 (m, 1H), 8.07 (m, 4H), 8.01-7.95 (m, 2H), 7.85-7.78 (m, 1H), 7.75-7.67 (m, 1H), 7.68-7.60 (m, 3H), 4.57 (d, J=5.7 Hz, 2H); MS (ESI(+)) m/e 393 (M+H)+.


Example 889
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}furan-2-carboxamide
Example 889A
tert-butyl 4-(2-(4-(5-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)furan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)furan-2-carboxamide for 4-bromoaniline.


Example 889B
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}furan-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(2-(4-(5-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)furan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.70 (s, 2H), 9.28 (t, J=6.1 Hz, 1H), 8.87 (d, J=6.7 Hz, 1H), 8.33 (s, 2H), 8.15 (d, J=2.1 Hz, 1H), 8.00 (s, 1H), 7.82 (s, 1H), 7.49 (dd, J=7.0, 1.5 Hz, 1H), 7.26 (d, J=3.5 Hz, 1H), 6.72 (d, J=3.5 Hz, 1H), 4.73-4.59 (m, 4H), 3.66-3.56 (m, 2H), 3.41 (d, J=11.4 Hz, 8H); MS (ESI(+)) m/e 420 (M+H)+.


Example 892
5-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 857, substituting methylhydrazine for benzylhydrazine in Example 857B. 1H NMR (300 MHz, DMSO-d6) δ 9.04 (t, J=6.0 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 7.89 (s, 1H), 7.73 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.30 (d, J=3.8 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.32 (s, 1H), 4.47 (d, J=5.9 Hz, 2H), 3.84 (s, 3H), 1.97-1.84 (m, 1H), 1.04-0.89 (m, 2H), 0.75-0.63 (m, 2H); MS (ESI(+)) m/e 378 (M+H)+.


Example 893
5-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 857, substituting (2-methoxyethyl)hydrazine for benzylhydrazine in Example 857B. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.04 (t, J=6.0 Hz, 1H), 8.49 (dd, J=7.0, 1.0 Hz, 1H), 7.89 (s, 1H), 7.73 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J=3.8 Hz, 1H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.31 (s, 1H), 4.47 (d, J=5.9 Hz, 2H), 4.33 (t, J=5.5 Hz, 2H), 3.73 (t, J=5.5 Hz, 2H), 3.24 (s, 3H), 2.00-1.87 (m, 1H), 1.01-0.92 (m, 2H), 0.72-0.63 (m, 2H); MS (ESI(+)) m/e 422 (M+H)+.


Example 894
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide
Example 894A
tert-butyl 4-(2-(4-(5-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)thiophen-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline.


Example 894B
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-5-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(2-(4-(5-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)thiophen-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.52 (s, 2H), 9.28-9.17 (m, 2H), 8.68 (d, J=1.2 Hz, 1H), 8.36-8.30 (m, 1H), 8.27 (d, J=0.4 Hz, 1H), 8.05 (d, J=1.4 Hz, 1H), 7.91 (d, J=0.5 Hz, 1H), 7.81 (d, J=3.9 Hz, 1H), 7.27 (d, J=3.9 Hz, 1H), 4.71-4.48 (m, 2H), 4.07 (s, 8H), 3.37 (s, 4H); MS (ESI(+)) m/e 437 (M+H)+.


Example 897
N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(phenylsulfonyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(phenylsulfonyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.38 (t, J=5.8 Hz, 1H), 9.11 (s, 1H), 8.61-8.57 (m, 1H), 8.18 (s, 1H), 8.16-8.03 (m, 4H), 8.04-7.97 (m, 2H), 7.93-7.89 (m, 1H), 7.76-7.68 (m, 1H), 7.70-7.61 (m, 2H), 4.60 (d, J=5.7 Hz, 2H); MS (ESI(+)) m/e 393 (M+H)+.


Example 898
N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyridin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(phenylsulfonyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.47 (t, J=5.8 Hz, 1H), 8.82 (s, 1H), 8.35-8.30 (m, 1H), 8.19-8.14 (m, 1H), 8.12-8.08 (m, 4H), 8.05-7.88 (m, 4H), 7.76-7.68 (m, 1H), 7.68-7.60 (m, 2H), 4.61 (d, J=5.8 Hz, 2H); MS (ESI(+)) m/e 392 (M+H)+.


Example 899
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting 1-isobutyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.24 (t, J=5.9 Hz, 1H), 8.51 (dd, J=7.0, 0.7 Hz, 1H), 7.90 (d, J=0.8 Hz, 1H), 7.87 (d, J=3.9 Hz, 1H), 7.57-7.49 (m, 2H), 7.43 (s, 1H), 7.39 (d, J=3.9 Hz, 1H), 6.87 (dd, J=7.0, 1.6 Hz, 1H), 6.56 (d, J=1.9 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 4.08 (d, J=7.4 Hz, 2H), 2.09 (dp, J=13.8, 6.9 Hz, 1H), 0.80 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 380 (M+H)+.


Example 900
tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 3-methylbutan-1-amine and 2-(imidazo[1,2-a]pyridin-7-yl)acetic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.16 (s, 1H), 8.55 (d, J=6.9 Hz, 1H), 7.97 (s, 1H), 7.65-7.53 (m, 2H), 7.53-7.47 (m, 2H), 7.20-7.13 (m, 2H), 7.01-6.95 (m, 1H), 4.09-4.00 (m, 2H), 3.72 (s, 2H), 2.87-2.55 (m, 3H), 1.76-1.67 (m, 2H), 1.50-1.35 (m, 11H); MS (ESI(+)) m/e 435 (M+H)+.


Example 901
N-[(3-chloroimidazo[1,2-a]pyrazin-6-yl)methyl]-4-[(cyclopentylacetyl)amino]benzamide

The title compound was prepared as described in Example 396, substituting 4-(2-cyclopentylacetamido)-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide for 4-(3-imidazo[1,2-a]pyridin-6-ylureido)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.07 (s, 1H), 9.09 (s, 1H), 8.95 (t, J=5.7 Hz, 1H), 8.28 (s, 1H), 7.95 (s, 1H), 7.87-7.81 (m, 2H), 7.69-7.63 (m, 2H), 4.61 (d, J=5.6 Hz, 2H), 2.38-2.12 (m, 3H), 1.80-1.64 (m, 2H), 1.66-1.40 (m, 4H), 1.25-1.09 (m, 2H); MS (ESI(+)) m/e 412 (M+H)+.


Example 902
N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide
Example 902A
2-(imidazo[1,2-a]pyridin-7-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 902B
N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide

The title compound was prepared as described in Example 1A, substituting 2-(imidazo[1,2-a]pyridin-7-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and 2,4-difluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.29 (s, 1H), 8.84 (d, J=6.9 Hz, 1H), 8.31 (d, J=1.9 Hz, 1H), 8.14 (d, J=2.1 Hz, 1H), 7.89 (s, 1H), 7.56-7.47 (m, 3H), 7.47-7.40 (m, 1H), 7.42-7.31 (m, 1H), 7.23-7.15 (m, 3H), 4.68-4.60 (m, 1H), 3.95 (bs, 2H), 3.58-3.44 (m, 1H), 3.26-3.09 (m, 1H), 2.94-2.70 (m, 2H), 1.94-1.81 (m, 1H), 1.79-1.40 (m, 3H); MS (ESI(+)) m/e 475 (M+H)+.


Example 903
2-(imidazo[1,2-a]pyridin-7-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}acetamide

The title compound was prepared as described in Example 1A, substituting 2-(imidazo[1,2-a]pyridin-7-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.28 (s, 1H), 8.84 (d, J=6.9 Hz, 1H), 8.34-8.28 (m, 1H), 8.18-8.14 (m, 1H), 7.89 (s, 1H), 7.55-7.43 (m, 3H), 7.22-7.16 (m, 2H), 4.60-4.50 (m, 1H), 4.09-4.00 (m, 1H), 3.96 (s, 2H), 3.18-3.01 (m, 1H), 2.96-2.82 (m, 1H), 2.79-2.67 (m, 1H), 2.63-2.50 (m, 1H), 1.87-1.70 (m, 2H), 1.57-1.30 (m, 2H), 1.07-0.93 (m, 6H); MS (ESI(+)) m/e 405 (M+H)+.


Example 904
1-[(3-chloroimidazo[1,2-a]pyridin-7-yl)methyl]-3-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}urea

The title compound was prepared as described in Example 396, substituting 1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-(4-(1-isobutyrylpiperidin-4-yl)phenyl)urea for 4-(3-imidazo[1,2-a]pyridin-6-ylureido)-N-((tetrahydro-2H-pyran-2-yl)methyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.31 (bs, 1H), 8.24 (d, J=7.0 Hz, 1H), 7.58 (s, 1H), 7.46 (s, 1H), 7.35-7.29 (m, 2H), 7.12-7.02 (m, 3H), 6.62-6.55 (m, 1H), 4.38 (d, J=6.0 Hz, 2H), 4.36-4.19 (m, 2H), 2.93-2.62 (m, 4H), 1.85-1.77 (m, 2H), 1.53-1.37 (m, 2H), 1.03 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 454 (M+H)+.


Example 905
N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide

The title compound was prepared as described in Example 1A, substituting 2-(imidazo[1,2-a]pyridin-7-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.75 (d, J=7.0 Hz, 1H), 8.18 (d, J=2.2 Hz, 1H), 8.00 (d, J=2.2 Hz, 1H), 7.89 (s, 1H), 7.56-7.35 (m, 5H), 7.33-7.25 (m, 1H), 7.25-7.17 (m, 3H), 4.83-4.74 (m, 1H), 3.99 (s, 2H), 3.68-3.59 (m, 1H), 3.31-3.18 (m, 1H), 3.03-2.76 (m, 2H), 2.00-1.92 (m, 1H), 1.87-1.51 (m, 3H); MS (ESI(+)) m/e 457 (M+H)+.


Example 906
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-methyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 857, substituting 4-methylpent-1-yne for ethynylcyclopropane in Example 857A and methylhydrazine for benzylhydrazine in Example 857B. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (t, J=5.9 Hz, 1H), 8.49 (dd, J=6.9, 0.9 Hz, 1H), 7.89 (s, 1H), 7.74 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.40 (s, 1H), 7.35 (d, J=3.8 Hz, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 6.46 (s, 1H), 4.48 (d, J=5.9 Hz, 2H), 3.75 (s, 3H), 2.54-2.51 (m, 2H), 1.96-1.84 (m, 1H), 0.94 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 394 (M+H)+.


Example 907
5-[1-benzyl-3-(2-methylpropyl)-1H-pyrazol-5-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 857, substituting 4-methylpent-1-yne for ethynylcyclopropane in Example 857A. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.05 (t, J=5.8 Hz, 1H), 8.49 (dd, J=7.0, 0.9 Hz, 1H), 7.89 (s, 1H), 7.76 (d, J=3.9 Hz, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.42-7.38 (m, 2H), 7.37-7.23 (m, 3H), 7.17-7.11 (m, 2H), 6.85 (dd, J=7.0, 1.7 Hz, 1H), 6.56 (s, 1H), 5.35 (bs, 2H), 4.48 (d, J=5.9 Hz, 2H), 2.49-2.45 (m, 2H), 1.87-1.74 (m, 1H), 0.87 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 470 (M+H)+.


Example 908
4-[(cyclopentylacetyl)amino]-2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)-2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.27 (s, 1H), 9.13 (s, 1H), 8.73-8.65 (m, 1H), 8.59-8.56 (m, 1H), 8.24 (s, 1H), 7.94-7.91 (m, 1H), 7.75-7.67 (m, 2H), 7.34 (dd, J=8.5, 1.9 Hz, 1H), 4.59 (d, J=5.8 Hz, 2H), 2.37-2.32 (m, 2H), 2.32-2.16 (m, 1H), 1.82-1.68 (m, 2H), 1.67-1.44 (m, 4H), 1.26-1.10 (m, 2H); MS (ESI(+)) m/e 396 (M+H)+.


Example 909
N-(2,5-difluorobenzyl)-N′-(imidazo[1,2-a]pyridin-7-ylmethyl)benzene-1,4-dicarboxamide

The title compound was prepared as described in Example 1A, substituting 2,5-difluorobenzyl amine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.42 (t, J=5.9 Hz, 1H), 9.20 (t, J=5.8 Hz, 1H), 8.83 (d, J=6.9 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.10 (d, J=2.0 Hz, 1H), 8.04-8.00 (m, 4H), 7.78 (s, 1H), 7.45 (dd, J=6.9, 1.6 Hz, 1H), 7.32-7.12 (m, 3H), 4.69 (d, J=5.8 Hz, 2H), 4.52 (d, J=5.7 Hz, 2H); MS (ESI(+)) m/e 421 (M+H)+.


Example 910
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{[2-(propan-2-yl)pyrrolidin-1-yl]carbonyl}benzamide

The title compound was prepared as described in Example 1A, substituting (propan-2-yl)pyrrolidine for 3-methylbutan-1-amine and 4-(imidazo[1,2-a]pyridin-7-ylmethylcarbamoyl)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.44-9.36 (m, 1H), 8.86 (d, J=6.9 Hz, 1H), 8.31 (d, J=2.1 Hz, 1H), 8.14 (d, J=2.1 Hz, 1H), 8.01-7.95 (m, 2H), 7.80 (s, 1H), 7.65-7.59 (m, 2H), 7.49 (d, J=7.6 Hz, 1H), 4.69 (d, J=5.8 Hz, 2H), 4.15-4.05 (m, 1H), 3.47-3.19 (m, 2H), 2.39-2.26 (m, 1H), 1.96-1.57 (m, 4H), 0.93-0.85 (m, 6H); MS (ESI(+)) m/e 391 (M+H)+.


Example 911
N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-2-(imidazo[1,2-a]pyridin-7-yl)acetamide
Example 911A
N′-(3,3-dimethylbutanoyl)-4-nitrobenzohydrazide

A suspension of 4-nitrobenzohydrazide (0.500 g, 2.76 mmol), and 4-methylmorpholine (0.455 ml, 4.14 mmol) were stirred in dichloromethane (20 ml). 3,3-Dimethylbutanoyl chloride (0.422 ml, 3.04 mmol) was added and the reaction mixture was stirred for 2 hours. Normal phase chromatography of the crude reaction mixture gave the title compound.


Example 911B
2-neopentyl-5-(4-nitrophenyl)-1,3,4-oxadiazole

A mixture of N′-(3,3-dimethylbutanoyl)-4-nitrobenzohydrazide (0.556 g, 1.991 mmol) and methyl N-(triethylammoniumsulfonyl)carbamate (0.572 g, 2.389 mmol) in tetrahydrofuran (10 ml) was heated to 120° C. in a microwave (Biotage Initiator) for 45 minutes. The crude reaction mixture was concentrated and purified by normal phase chromatography to give the title compound.


Example 911C
4-(5-neopentyl-1,3,4-oxadiazol-2-yl)aniline

The title compound was prepared as described in Example 1B, substituting 2-neopentyl-5-(4-nitrophenyl)-1,3,4-oxadiazole for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.


Example 911D
N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-(5-neopentyl-1,3,4-oxadiazol-2-yl)aniline for tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate and 2-(imidazo[1,2-a]pyridin-7-yl)acetic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.55 (s, 1H), 8.49 (d, J=7.0 Hz, 1H), 7.96-7.89 (m, 3H), 7.86-7.79 (m, 2H), 7.53 (d, J=1.1 Hz, 1H), 7.49 (s, 1H), 6.88 (dd, J=7.0, 1.6 Hz, 1H), 3.77 (s, 2H), 2.82 (s, 2H), 1.02 (s, 9H); MS (ESI(+)) m/e 390 (M+H)+.


Example 912
tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate
Example 912A
tert-butyl 4-(4-amino-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-2-fluoroaniline for 4-bromoaniline.


Example 912B
tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-amino-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 912C
tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate for 4-amino-N-isopentylbenzamide and imidazo[1,2-a]pyridin-7-ylmethanamine for imidazo[1,2-a]pyridin-6-amine 1H NMR (400 MHz, DMSO-d6) δ ppm 8.49 (d, J=7.0 Hz, 1H), 8.37 (d, J=2.3 Hz, 1H), 7.97 (t, J=8.5 Hz, 1H), 7.88 (s, 1H), 7.52 (d, J=1.2 Hz, 1H), 7.39 (s, 1H), 7.12-7.04 (m, 2H), 7.00-6.94 (m, 1H), 6.82 (dd, J=7.0, 1.6 Hz, 1H), 4.35 (d, J=5.9 Hz, 2H), 4.10-4.01 (m, 2H), 2.89-2.56 (m, 3H), 1.77-1.68 (m, 2H), 1.41 (s, 11H); MS (ESI(+)) m/e 468 (M+H)+.


Example 958
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1068, substituting pyrrolidine-1-carbonyl chloride for piperidine-1-carbonyl chloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.28-9.21 (m, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.31 (d, J=2.1 Hz, 1H), 8.13 (d, J=2.1 Hz, 1H), 7.91-7.85 (m, 2H), 7.77 (s, 1H), 7.47 (dd, J=7.0, 1.6 Hz, 1H), 7.43-7.36 (m, 2H), 4.67 (d, J=5.8 Hz, 2H), 3.83-3.75 (m, 2H), 3.35-3.23 (m, 4H), 2.85-2.72 (m, 3H), 1.81-1.69 (m, 6H), 1.71-1.53 (m, 2H); MS (ESI(+)) m/e 432 (M+H)+.


Example 1067
tert-butyl 4-{3-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate for 3-methylbutan-1-amine and 2-(imidazo[1,2-a]pyridin-7-yl)acetic acid hydrochloride for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.97 (s, 1H), 8.58 (d, J=6.9 Hz, 1H), 8.00 (s, 1H), 7.77-7.67 (m, 2H), 7.58 (d, J=1.4 Hz, 1H), 7.15 (dd, J=12.2, 1.9 Hz, 1H), 7.06-6.99 (m, 2H), 4.10-4.01 (m, 2H), 3.82 (bs, 2H), 2.94-2.58 (m, 3H), 1.78-1.69 (m, 2H), 1.53-1.36 (m, 11H); MS (ESI(+)) m/e 453 (M+H)+.


Example 1068
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(piperidin-1-ylcarbonyl)piperidin-4-yl]benzamide

A solution of piperidine-1-carbonyl chloride (0.033 g, 0.224 mmol) in N-methyl-2-pyrrolidinone (1 mL) was treated with N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(piperidin-4-yl)-benzamide (0.05 g, 0.150 mmol) and triethylamine (0.042 ml, 0.299 mmol) and the reaction mixture was stirred at room temperature for 18 hours. The mixture was purified by reverse-phase HPLC to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.24 (t, J=5.9 Hz, 1H), 8.84 (d, J=7.0 Hz, 1H), 8.30 (d, J=2.1 Hz, 1H), 8.13 (d, J=2.1 Hz, 1H), 7.91-7.84 (m, 2H), 7.76 (s, 1H), 7.50-7.44 (m, 1H), 7.42-7.36 (m, 2H), 4.67 (d, J=5.8 Hz, 2H), 3.71-3.62 (m, 2H), 3.16-3.10 (m, 4H), 2.89-2.68 (m, 3H), 1.81-1.72 (m, 2H), 1.68-1.44 (m, 8H); MS (ESI(+)) m/e 446 (M+H)+.


Example 1069
1-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
Example 1069A
1-(2-fluoro-4-(piperidin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(3-fluoro-4-{[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]amino}phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 1069B
1-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea

The title compound was prepared as described in Example 1A, substituting 1-(2-fluoro-4-(piperidin-4-yl)phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.73 (d, J=7.0 Hz, 1H), 8.16 (d, J=2.1 Hz, 1H), 7.99-7.95 (m, 1H), 7.85-7.77 (m, 2H), 7.50-7.39 (m, 6H), 7.11-6.99 (m, 2H), 4.84-4.72 (m, 1H), 4.60 (bs, 2H), 3.93-3.73 (m, 1H), 3.29-3.15 (m, 1H), 3.00-2.76 (m, 2H), 2.03-1.84 (m, 1H), 1.83-1.53 (m, 3H); MS (ESI(+)) m/e 472 (M+H)+.


Table 25.


The following Examples were prepared essentially as described in Example 1069, substituting an appropriate carboxylic acid in Example 1069B.














Ex
Name
MS







1070
1-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-
(ESI(+))



fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 452




(M + H)+


1071
1-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-
(ESI(+))



fluorophenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 466




(M + H)+


1072
1-{2-fluoro-4-[1-(4-methylpentanoyl)piperidin-4-
(ESI(+))



yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 466




(M + H)+


1073
1-(2-fluoro-4-{1-[(2S)-2-methylbutanoyl]piperidin-
(ESI(+))



4-yl}phenyl)-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 452




(M + H)+


1074
1-{2-fluoro-4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)
(ESI(+))



piperidin-4-yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-
m/e 480



ylmethyl)urea
(M + H)+


1075
1-{2-fluoro-4-[1-(pyridin-2-ylcarbonyl)piperidin-4-
(ESI(+))



yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 473




(M + H)+


1076
1-{4-[1-(2-cyanobenzoyl)piperidin-4-yl]-2-fluoro-
(ESI(+))



phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 497




(M + H)+


1078
1-{2-fluoro-4-[1-(2-methylpropanoyl)piperidin-4-
(ESI(+))



yl]phenyl}-3-(imidazo[1,2-a]pyridin-7-ylmethyl)urea
m/e 438




(M + H)+









Example 1077
4-{4-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]phenyl}-N,N-dimethylpiperidine-1-carboxamide

The title compound was prepared as described in Example 1068, substituting N,N-dimethylamine-1-carbonyl chloride for piperidine-1-carbonyl chloride. 1H NMR (400 MHz, methanol-d4) δ ppm 8.75 (d, J=7.0 Hz, 1H), 8.19-8.15 (m, 1H), 8.01-7.97 (m, 1H), 7.89-7.83 (m, 2H), 7.80 (s, 1H), 7.51-7.46 (m, 1H), 7.44-7.38 (m, 2H), 4.77 (s, 2H), 3.85-3.76 (m, 2H), 2.98-2.77 (m, 9H), 1.90-1.81 (m, 2H), 1.81-1.66 (m, 2H); MS (ESI(+)) m/e 406 (M+H)+.


Example 1079
4-[(cyclopentylacetyl)amino]-N-[(7-fluoroimidazo[1,2-a]pyridin-6-yl)methyl]benzamide

The title compound was prepared as described in Example 1A, substituting (7-fluoroimidazo[1,2-a]pyridin-6-yl)methanamine for 3-methylbutan-1-amine and 4-(2-cyclopentylacetamido)benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.08 (s, 1H), 8.87 (t, J=5.5 Hz, 1H), 8.56 (d, J=7.3 Hz, 1H), 7.96 (s, 1H), 7.88-7.82 (m, 2H), 7.71-7.64 (m, 2H), 7.52 (d, J=1.2 Hz, 1H), 7.46-7.39 (m, 1H), 4.49 (d, J=5.5 Hz, 2H), 2.36-2.30 (m, 2H), 2.31-2.15 (m, 1H), 1.81-1.68 (m, 2H), 1.68-1.43 (m, 4H), 1.26-1.10 (m, 2H); MS (ESI(+)) m/e 395 (M+H)+.


Example 1080
N-[(7-fluoroimidazo[1,2-a]pyridin-6-yl)methyl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting (7-fluoroimidazo[1,2-a]pyridin-6-yl)methanamine for 3-methylbutan-1-amine and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.93 (t, J=5.5 Hz, 1H), 8.58 (d, J=7.7 Hz, 1H), 8.14 (d, J=0.8 Hz, 1H), 7.98 (s, 1H), 7.80 (d, J=0.8 Hz, 1H), 7.73 (d, J=3.8 Hz, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.44 (d, J=11.0 Hz, 1H), 7.21 (d, J=3.8 Hz, 1H), 4.48 (d, J=5.5 Hz, 2H), 3.92 (d, J=7.2 Hz, 2H), 2.21-2.05 (m, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 398 (M+H)+.


Example 1081
N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-2-(imidazo[1,2-a]pyridin-7-yl)acetamide
Example 1081A
N-(2-fluoro-4-(piperidin-4-yl)phenyl)-2-(imidazo[1,2-a]pyridin-7-yl)acetamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-{3-fluoro-4-[(imidazo[1,2-a]pyridin-7-ylacetyl)amino]phenyl}piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 1081B
N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-2-(imidazo[1,2-a]pyridin-7-yl)acetamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-2-(imidazo[1,2-a]pyridin-7-yl)acetamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.75 (dd, J=6.9, 0.9 Hz, 1H), 8.19 (dd, J=2.2, 0.8 Hz, 1H), 8.00 (d, J=2.2 Hz, 1H), 7.91 (s, 1H), 7.78 (t, J=8.2 Hz, 1H), 7.53-7.38 (m, 6H), 7.16-7.04 (m, 2H), 4.83-4.69 (m, 1H), 4.06 (s, 2H), 3.91-3.79 (m, 1H), 3.30-3.14 (m, 1H), 3.03-2.81 (m, 2H), 2.07-1.54 (m, 4H); MS (ESI(+)) m/e 457 (M+H)+.


Example 1154
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(pyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide

The title compound was prepared as described in Example 51A, substituting 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-yl)pyrimidine for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO d6) δ ppm 9.32 (t, J=5.9 Hz, 1H), 8.90-8.80 (m, 2H), 8.38 (dd, J=7.5, 1.2 Hz, 1H), 8.31 (d, J=2.0 Hz, 1H), 8.14 (d, J=2.1 Hz, 1H), 7.95 (d, J=8.5 Hz, 2H), 7.80 (s, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.47 (dd, J=7.0, 1.5 Hz, 1H), 7.32-7.18 (m, 1H), 6.48-6.40 (m, 1H), 4.68 (d, J=5.8 Hz, 2H), 4.57-4.47 (m, 2H), 4.19-4.04 (m, 2H), 2.74-2.64 (m, 2H); MS (ESI(+)) m/e 411 (M+H)+.


Example 1155
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-[1-(2-methylpyrimidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl]benzamide

The title compound was prepared as described in Example 51A, substituting 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-yl)pyrimidine for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07-8.95 (m, 1H), 8.78 (dd, J=7.0, 0.5 Hz, 1H), 8.28-8.16 (m, 2H), 8.00 (d, J=2.0 Hz, 1H), 7.97-7.87 (m, 2H), 7.80-7.74 (m, 1H), 7.63-7.54 (m, 2H), 7.40 (dd, J=7.0, 1.5 Hz, 1H), 7.04 (d, J=7.4 Hz, 1H), 6.41-6.31 (m, 1H), 4.66 (m, 2H), 4.47 (m, 2H), 4.10 (t, J=5.8 Hz, 2H), 2.77-2.64 (m, 2H), 2.55 (s, 3H); MS (ESI(+)) m/e 425 (M+H)+.


Example 1156
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-{1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,2,3,6-tetrahydropyridin-4-yl}benzamide

The title compound was prepared as described in Example 51A, substituting 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-1(2H)-yl)-6-(trifluoromethyl)pyrimidine for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide for 4-bromoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.30 (t, J=5.9 Hz, 1H), 8.84 (d, J=6.9 Hz, 1H), 8.68 (s, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.11 (d, J=2.1 Hz, 1H), 7.99-7.89 (m, 2H), 7.77 (s, 1H), 7.72-7.58 (m, 2H), 7.45 (dd, J=7.0, 1.5 Hz, 1H), 7.38-7.20 (m, 1H), 6.43 (m, 1H), 4.67 (d, J=5.8 Hz, 2H), 4.53-4.31 (m, 2H), 4.13-3.92 (m, 2H), 2.70-2.62 (m, 2H); MS (ESI(+)) m/e 479 (M+H)+.


Example 1157
5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide
Example 1157A
5-bromo-3,7-dimethyltricyclo[3.3.1.13,7]decane-1-carboxylic acid

In a 50 mL round-bottomed flask, bromine (3 mL) was cooled to 0° C. and iron (0.56 g) was added. The mixture was stirred at 0° C. for 30 minutes. 3,5-Dimethyladamantane-1-carboxylic acid (0.5 g) was added. The mixture was stirred at room temperature overnight. After adding ice and 6N aqueous HCl (10 mL), ethyl acetate (20 mL), and saturated aqueous sodium sulfite were added. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with saturated sodium sulfite and dried over sodium sulfate. After filtration and removal of the solvent, the product was used directly in the next step.


Example 1157B
5-bromo-3,7-dimethyltricyclo[3.3.1.13,7]dec-1-ylmethanol

To a solution of 5-bromo-3,7-dimethyltricyclo[3.3.1.13,7]decane-1-carboxylic acid (4.57 g, 15.9 mmol) in tetrahydrofuran (10 mL) was added borane tetrahydrofuran complex (50 mL, 1 M in THF) dropwise and the mixture was stirred at room temperature for 14 hours. The reaction mixture was quenched with methanol, concentrated and purified by normal phase chromatography to provide the title compound.


Example 1157C
1-(5-bromo-3,7-dimethyltricyclo[3.3.1.13,7]dec-1-yl)-1H-pyrazole

To a solution of the 5-bromo-3,7-dimethyltricyclo[3.3.1.13,7]dec-1-ylmethanol (8.0 g, 29.3 mmol) in toluene (60 mL) was added 1H-pyrazole (1.55 g, 22.7 mmol) and cyanomethylenetributylphosphorane (2.0 g, 29.3 mmol) under nitrogen. After the addition, the mixture was stirred at 90° C. overnight. The reaction mixture was then concentrated, and the residue was purified by normal phase chromatography to give the title compound.


Example 1157D
2-{[3,5-dimethyl-7-(1H-pyrazol-1-ylmethyl)tricyclo[3.3.1.13,7]dec-1-yl]oxy}ethanol

To a solution of 1-(5-bromo-3,7-dimethyltricyclo[3.3.1.13,7]dec-1-yl)-1H-pyrazole (4.5 g) in ethane-1,2-diol (12 mL) was added triethylamine (3 mL) under nitrogen. The mixture was heated to 150° C. in a Biotage Initiator microwave reactor for 45 minutes. The mixture was poured over water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried with sodium sulfate, filtered and concentrated. The residue was purified by normal phase chromatography to give the title compound.


Example 1157E
2-({3,5-dimethyl-7-[(5-methyl-1H-pyrazol-1-yl)methyl]tricyclo[3.3.1.13,7]dec-1-yl}oxy)ethanol

To a cold (−78° C.) solution of the 2-{[3,5-dimethyl-7-(1H-pyrazol-1-ylmethyl)tricyclo[3.3.1.13,7]dec-1-yl]oxy}ethanol (3.69 g) in tetrahydrofuran (50 mL) was added n-butyllithium (20 mL, 2.5 M in hexane) under nitrogen. The mixture was stirred at −78° C. for 1.5 hours. Iodomethane (10 mL) was added by syringe, and the mixture was stirred for an additional 3 hours. The reaction mixture was then quenched by the addition of aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried with sodium sulfate, filtered and concentrated. The residue was purified by normal phase chromatography to give the title compound.


Example 1157F
1-({3,5-dimethyl-7-[2-(hydroxy)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-4-iodo-5-methyl-1H-pyrazole

To a solution of the 2-({3,5-dimethyl-7-[(5-methyl-1H-pyrazol-1-yl)methyl]tricyclo[3.3.1.13,7]dec-1-yl}oxy)ethanol (3.5 g, 11 mmol) in N,N-dimethylformamide (30 ml) was added N-iodosuccinimide (3.2 g, 14.22 mmol). The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was then diluted with ethyl acetate and washed with aqueous sodium thiosulfate, water and brine. After drying over anhydrous sodium sulfate, the mixture was filtered and concentrated. The residue was purified by normal phase chromatography to give the title compound.


Example 1157G
2-({3-[(4-iodo-5-methyl-1H-pyrazol-1-yl)methyl]-5,7-dimethyltricyclo[3.3.1.13,7]dec-1-yl}oxy)ethyl methanesulfonate

To a cold (0° C.) solution of 1-({3,5-dimethyl-7-[2-(hydroxy)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-4-iodo-5-methyl-1H-pyrazole (2.1 g) in methylene chloride (30 mL) was added triethylamine (1.42 g) followed by methanesulfonyl chloride (0.542 g). The mixture was stirred at room temperature for 1.5 hours and then was diluted with ethyl acetate. The layers were separated, and the organic layer was washed with water and brine, dried with sodium sulfate, filtered and concentrated to give the title compound, which was used in the next step without further purification.


Example 1157H
1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-4-iodo-5-methyl-1H-pyrazole

A solution of 2-({3-[(4-iodo-5-methyl-1H-pyrazol-1-yl)methyl]-5,7-dimethyltricyclo[3.3.1.13,7]dec-1-yl}oxy)ethyl methanesulfonate (2.5 g) in 2 M methylamine in methanol (15 mL) was heated to 100° C. for 20 minutes in a Biotage Initiator microwave reactor. The reaction mixture was concentrated, and the residue was diluted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, water and brine. The organic layer was dried with sodium sulfate, filtered and concentrated to give the title compound which was used in the next reaction without further purification.


Example 11571
tert-butyl[2-({3-[(4-iodo-5-methyl-1H-pyrazol-1-yl)methyl]-5,7-dimethyltricyclo[3.3.1.13,7]dec-1-yl]oxy)ethyl}methylcarbamate

To a solution of 1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-4-iodo-5-methyl-1H-pyrazole (2.2 g) in tetrahydrofuran (30 mL) was added Boc-anhydride (1.26 g) and a catalytic amount of 4-dimethylaminopyridine. The mixture was stirred at room temperature for 1.5 hours and diluted with ethyl acetate. The solution was washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified by normal phase chromatography to give the title compound


Example 1157J
tert-butyl {2-[(3,5-dimethyl-7-{[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]methyl}tricyclo[3.3.1.13,7]dec-1-yl)oxy]ethyl}methylcarbamate

To a solution of tert-butyl[2-({3-[(4-iodo-5-methyl-1H-pyrazol-1-yl)methyl]-5,7-dimethyltricyclo[3.3.1.13,7]dec-1-yl]oxy)ethyl}methylcarbamate (2.8 g, 5.02 mmol) in dioxane (40 ml) was added bis(benzonitrile)palladium(II) chloride (96 mg, 0.251 mmol), S-Phos (206 mg, 0.502 mmol), and pinacolborane (2 mL) followed by triethylamine (2.5 mL, 5.25 mmol) under nitrogen. The mixture was stirred at reflux overnight. The reaction mixture was then diluted with ethyl acetate and washed with water and brine. After drying (anhydrous sodium sulfate), the solution was filtered and concentrated and the residue was purified by normal phase chromatographyto give the title compound.


Example 1157K
5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

The title compound was prepared as described in Example 51A, substituting tert-butyl {2-[(3,5-dimethyl-7-{[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]methyl}tricyclo[3.3.1.13,7]dec-1-yl)oxy]ethyl}methylcarbamate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromo-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide for 4-bromoaniline followed by deprotection as described in Example 28A. 1H NMR (400 MHz, DMSO-d6) δ 9.50 (t, J=5.9 Hz, 1H), 8.88 (d, J=7.0 Hz, 1H), 8.76-8.64 (m, 2H), 8.34 (d, J=2.0 Hz, 1H), 8.16 (d, J=2.1 Hz, 1H), 7.93 (d, J=3.9 Hz, 1H), 7.83 (s, 1H), 7.76 (s, 1H), 7.49 (dd, J=7.0, 1.3 Hz, 1H), 7.23 (d, J=3.9 Hz, 1H), 4.65 (d, J=5.8 Hz, 2H), 3.92 (s, 2H), 3.63-3.55 (m, 2H), 3.04-2.91 (m, 2H), 2.51 (dd, J=6.0, 3.7 Hz, 3H), 2.45 (s, 3H), 1.42 (s, 2H), 1.31 (dd, J=27.3, 11.4 Hz, 4H), 1.16 (q, J=12.5 Hz, 4H), 1.07-0.99 (m, 2H), 0.87 (s, 6H); MS (ESI(+)) m/e 587 (M+H)+.


Example 1158
2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide
Example 1158A
tert-butyl 4-(3-fluoro-4-(methoxycarbonyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 51A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and methyl 4-bromo-2-fluorobenzoate for 4-bromoaniline.


Example 1158B
tert-butyl 4-(3-fluoro-4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(3-fluoro-4-(methoxycarbonyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate for N-isopentyl-4-nitrobenzamide.


Example 1158C
4-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-fluorobenzoic acid

The title compound was prepared as described in Example 4B, substituting tert-butyl 4-(3-fluoro-4-(methoxycarbonyl)phenyl)piperidine-1-carboxylate for methyl 4-(3-imidazo[1,2-a]pyridin-6-ylureido)benzoate.


Example 1158D
tert-butyl 4-(3-fluoro-4-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting imidazo[1,2-a]pyrazin-6-ylmethanamine for 3-methylbutan-1-amine and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-fluorobenzoic acid for 4-nitrobenzoic acid.


Example 1158E
2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(3-fluoro-4-((imidazo[1,2-a]pyrazin-6-ylmethyl)carbamoyl)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 1158F
2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}benzamide

The title compound was prepared as described in Example 1A, substituting 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 1-methylcyclopropanecarboxylic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.27 (s, 1H), 8.72 (s, 1H), 8.28 (d, J=1.5 Hz, 1H), 8.11 (d, J=1.6 Hz, 1H), 7.78 (t, J=7.9 Hz, 1H), 7.27-7.11 (m, 2H), 4.79 (s, 2H), 4.63-4.51 (m, 2H), 3.23-2.72 (m, 3H), 1.99-1.88 (m, 2H), 1.71-1.54 (m, 2H), 1.33 (s, 3H), 1.02-0.83 (m, 2H), 0.73-0.55 (m, 2H); MS (ESI(+)) m/e 436 (M+H)+.


Example 1159
4-(1-benzoylpiperidin-4-yl)-2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)benzamide

The title compound was prepared as described in Example 1A, substituting 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and benzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.28-9.20 (m, 1H), 8.74-8.65 (m, 1H), 8.30-8.21 (m, 1H), 8.13-8.05 (m, 1H), 7.79 (t, J=7.9 Hz, 1H), 7.51-7.40 (m, 5H), 7.29-7.14 (m, 2H), 4.85-4.72 (m, 3H), 3.94-3.76 (m, 1H), 3.30-3.14 (m, 1H), 3.05-2.86 (m, 2H), 2.07-1.60 (m, 4H); MS (ESI(+)) m/e 458 (M+H)+.


Example 1160
2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and isobutyric acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.26 (s, 1H), 8.75-8.66 (m, 1H), 8.31-8.22 (m, 1H), 8.14-8.06 (m, 1H), 7.78 (t, J=8.0 Hz, 1H), 7.27-7.10 (m, 2H), 4.79 (s, 2H), 4.75-4.66 (m, 1H), 4.26-4.14 (m, 1H), 3.29-3.15 (m, 1H), 3.09-2.86 (m, 2H), 2.79-2.61 (m, 1H), 2.05-1.85 (m, 2H), 1.74-1.48 (m, 2H), 1.18-1.05 (m, 6H); MS (ESI(+)) m/e 424 (M+H)+.


Example 1161
2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting 2-fluoro-N-(imidazo[1,2-a]pyrazin-6-ylmethyl)-4-(piperidin-4-yl)benzamide for 3-methylbutan-1-amine and 3,3,3-trifluoropropanoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.24 (s, 1H), 8.74-8.65 (m, 1H), 8.30-8.21 (m, 1H), 8.13-8.04 (m, 1H), 7.78 (t, J=7.9 Hz, 1H), 7.27-7.10 (m, 2H), 4.78 (s, 2H), 4.72-4.64 (m, 1H), 4.14-4.00 (m, 1H), 3.63-3.45 (m, 2H), 3.30-3.21 (m, 1H), 3.03-2.86 (m, 1H), 2.77 (m, 1H), 1.98-1.86 (m, 2H), 1.65 (m, 2H); MS (ESI(+)) m/e 464 (M+H)+.


Example 1162
N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)acetamide
Example 1162A
tert-butyl 4-(4-(2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)acetamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for 3-methylbutan-1-amine and 2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)acetic acid hydrochloride for 4-nitrobenzoic acid.


Example 1162B
2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide

The title compound was prepared as described in Example 28A, substituting tert-butyl 4-(4-(2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)acetamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(3-imidazo[1,2-a]pyridin-6-ylureido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate.


Example 1162C
N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)acetamide

The title compound was prepared as described in Example 1A, substituting 2-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-N-(4-(piperidin-4-yl)phenyl)acetamide for 3-methylbutan-1-amine and 2-fluorobenzoic acid for 4-nitrobenzoic acid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 10.28-10.20 (m, 1H), 9.30 (s, 1H), 8.54 (s, 1H), 7.85-7.74 (m, 1H), 7.63-7.46 (m, 4H), 7.41-7.31 (m, 3H), 7.31-7.20 (m, 2H), 4.77-4.65 (m, 1H), 3.75 (s, 2H), 3.56-3.46 (m, 1H), 3.30-3.15 (m, 1H), 2.99-2.75 (m, 2H), 1.97-1.86 (m, 1H), 1.81-1.49 (m, 3H); MS (ESI(+)) m/e 458 (M+H)+.


Example 1163
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

A solution of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide (0.100 g, 0.197 mmol) in N,N-dimethylformamide (2 ml) was added tert-butyl 4-(2-bromoethyl)piperazine-1-carboxylate (0.058 g, 0.197 mmol) followed by N,N-diisopropylethylamine (0.138 ml, 0.788 mmol) and the reaction was stirred overnight. The reaction mixture was purified directly using normal phase chromatography and the resulting material was treated with HCl in dioxane (4M) for 2 hours then concentrated to give the title compound as a hydrochloride salt. 1H NMR (500 MHz, DMSO-d6) δ 14.64 (s, 1H), 10.40 (s, 1H), 9.72 (s, 1H), 9.54 (t, J=6.0 Hz, 1H), 8.89 (d, J=6.9 Hz, 1H), 8.34 (d, J=1.8 Hz, 1H), 8.22 (s, 1H), 8.16 (d, J=2.1 Hz, 1H), 7.91 (d, J=3.9 Hz, 1H), 7.87 (s, 1H), 7.83 (s, 1H), 7.50 (dd, J=7.0, 1.4 Hz, 1H), 7.28 (d, J=3.8 Hz, 1H), 4.64 (d, J=5.8 Hz, 2H), 4.23-3.54 (m, 10H), 3.35 (d, J=38.3 Hz, 8H), 1.72 (d, J=77.7 Hz, 4H), 0.98 (s, 3H); MS (ESI(+)) m/e 547 (M+H)+.


Example 1164
S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine

A suspension of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide (0.100 g, 0.197 mmol) and 4-methylmorpholine (0.108 ml, 0.985 mmol) in N,N-diisopropylethylamine (0.5 ml) was added to 2,5-dioxopyrrolidin-1-yl 2-bromoacetate (0.056 g, 0.236 mmol) in N,N-diisopropylethylamine (0.5 ml) and stirred at room temperature. After 1 hour, (R)-2-amino-3-mercaptopropanoic acid (0.119 g, 0.985 mmol) as a solution in water (1 ml) was added. After stirring an additional 1 hour, a few drops of TFA were added to form a homogeneous solution which was purified by revere phase chromatography. The product containing peaks were lyophilized to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.30 (t, J=6.0 Hz, 1H), 8.86 (d, J=7.0 Hz, 1H), 8.44 (bs, 2H), 8.32 (d, J=2.0 Hz, 1H), 8.18-8.11 (m, 2H), 7.86-7.77 (m, 3H), 7.46 (dd, J=7.0, 1.5 Hz, 1H), 7.27 (dd, J=3.7, 1.8 Hz, 1H), 4.65 (d, J=5.8 Hz, 2H), 4.21-4.13 (m, 1H), 4.13-4.02 (m, 2H), 4.02-3.92 (m, 1H), 3.87-3.57 (m, 3H), 3.42-3.29 (m, 1H), 3.29-3.18 (m, 1H), 3.10 (dd, J=14.6, 4.7 Hz, 1H), 2.98 (dd, J=14.6, 7.6 Hz, 1H), 1.60-1.18 (m, 4H), 0.96 (s, 3H); MS (ESI(+)) m/e 596 (M+H)+.


Example 1165
5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin-4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide

A suspension of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide (0.139 g, 0.274 mmol), 2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azaicosan-20-oic acid (0.100 g, 0.274 mmol), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.104 g, 0.274 mmol) and 4-methylmorpholine (0.105 ml, 0.958 mmol) was stirred at room temperature for 3 hours. The reaction mixture was purified directly by normal phase chromatography and the resulting material was treated with HCl/dioxane (4 M) then concentrated to give the title compound as a hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) δ 14.71 (s, 1H), 9.58 (t, J=6.0 Hz, 1H), 8.89 (d, J=7.0 Hz, 1H), 8.35 (d, J=1.9 Hz, 1H), 8.16 (d, J=2.1 Hz, 2H), 8.06 (s, 3H), 7.92 (d, J=3.9 Hz, 1H), 7.83 (s, 2H), 7.50 (dd, J=7.0, 1.2 Hz, 1H), 7.26 (d, J=3.8 Hz, 1H), 4.64 (d, J=5.8 Hz, 2H), 4.05 (s, 2H), 3.80 (dd, J=11.8, 6.8 Hz, 2H), 3.66-3.58 (m, 4H), 3.55 (dd, J=9.2, 4.4 Hz, 4H), 3.50 (t, J=7.5 Hz, 8H), 3.37-3.26 (m, 1H), 3.23-3.13 (m, 1H), 2.99-2.90 (m, 2H), 2.55 (t, J=6.6 Hz, 2H), 1.53-1.19 (m, 4H), 0.95 (s, 3H); MS (ESI(+)) m/e 682 (M+H)+.


Example 1166
S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine

A suspension of N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}thiophene-2-carboxamide (0.050 g, 0.099 mmol) and 4-methylmorpholine (0.054 ml, 0.493 mmol) in N,N-diisopropylethylamine (0.5 ml) was added to 2,5-dioxopyrrolidin-1-yl 3-(2-bromoacetamido)propanoate (0.036 g, 0.118 mmol) in N,N-diisopropylethylamine (0.5 ml) and the mixture was stirred at room temperature. After 1 hour, (R)-2-amino-3-mercaptopropanoic acid (0.060 g, 0.493 mmol) as a solution in water (1 ml) was added. After 1 hour, a few drops of TFA were added to form a homogeneous solution and the mixture was purified by chromatography to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.28 (t, J=5.9 Hz, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.47 (s, 2H), 8.30 (d, J=1.9 Hz, 1H), 8.21 (t, J=5.6 Hz, 1H), 8.17-8.09 (m, 2H), 7.84 (s, 1H), 7.81-7.74 (m, 2H), 7.44 (dd, J=7.0, 1.1 Hz, 1H), 7.27 (d, J=3.8 Hz, 1H), 4.65 (d, J=5.8 Hz, 2H), 4.20 (dd, J=7.5, 4.3 Hz, 1H), 4.06 (s, 2H), 3.90-3.78 (m, 2H), 3.35-2.94 (m, 8H), 2.59-2.41 (m, 2H), 1.57-1.19 (m, 4H), 0.95 (s, 3H); MS (ESI(+)) m/e 667 (M+H)+.

Claims
  • 1. A compound, or a therapeutically acceptable salt thereof, selected from the group consisting of: 5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[3.3.1.13,7]dec-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine;5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin-4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophene-2-carboxamide;S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-oxoethyl}-L-cysteine;
Parent Case Info

This application claims priority to U.S. Provisional Application Ser. No. 61/645,679, filed May 11, 2012, U.S. Provisional Application Ser. No. 61/718,998, filed Oct. 26, 2012, and U.S. Provisional Application Ser. No. 61/779,626, filed Mar. 13, 2013, which are incorporated by reference in their entirety.

US Referenced Citations (21)
Number Name Date Kind
7504412 Kishino et al. Mar 2009 B2
7511013 Molino et al. Mar 2009 B2
7514068 Tung Apr 2009 B2
7521421 Naicker et al. Apr 2009 B2
7528131 Persichetti et al. May 2009 B2
7531685 Czarnik May 2009 B2
7534814 Ascher et al. May 2009 B2
7538189 Naicker et al. May 2009 B2
20080051409 Gmeiner et al. Feb 2008 A1
20090082471 Czarnik Mar 2009 A1
20090088416 Czarnik Apr 2009 A1
20090093422 Tung et al. Apr 2009 A1
20090105147 Masse Apr 2009 A1
20090105307 Galley et al. Apr 2009 A1
20090105338 Czarnik Apr 2009 A1
20090111840 Herold et al. Apr 2009 A1
20090118238 Czarnik May 2009 A1
20090131363 Harbeson May 2009 A1
20090131485 Liu et al. May 2009 A1
20090137457 Harbeson May 2009 A1
20130303508 Clark et al. Nov 2013 A1
Foreign Referenced Citations (21)
Number Date Country
1657242 May 2006 EP
9507271 Mar 1995 WO
9710223 Mar 1997 WO
9748397 Dec 1997 WO
9748696 Dec 1997 WO
03080054 Oct 2003 WO
2005085252 Sep 2005 WO
2005099353 Oct 2005 WO
2006008754 Jan 2006 WO
2008025857 Mar 2008 WO
2009109610 Sep 2009 WO
2012031197 Mar 2012 WO
WO 2012031196 Mar 2012 WO
WO 2012137089 Oct 2012 WO
2012154194 Nov 2012 WO
WO 2013091011 Jun 2013 WO
WO 2013127266 Sep 2013 WO
WO 2013127267 Sep 2013 WO
WO 2013127268 Sep 2013 WO
WO 2013130935 Sep 2013 WO
WO 2013130943 Sep 2013 WO
Non-Patent Literature Citations (26)
Entry
Gentile; Bioorganic and Medicinal Chemistry Letters 2012, 22, 1989-1994.
Chemical Abstracts STN Record for RN 1297853-53-2, dated May 20, 2011.
Adya R., et al., “Nuclear Factor-kappaB Induction by Visfatin in Human Vascular Endothelial Cells: Its Role in MMP-2/9 Production and Activation,” Diabetes Care, 2008, vol. 31 (4), pp. 758-760.
Beylot, M. et al., “In Vivo Studies of Intrahepatic Metabolic Pathways,” Diabetes Metabolism, 1997, vol. 23 (3), pp. 251-257.
Blagojevic, N. et al., “Role of heavy water in Boron Neutron Capture Therapy,” Topics in Dosimetry & Treatment Planning for Neutron Capture Therapy, 1994, pp. 125-134.
Blake, M. I. et al., “Studies With Deuterated Drugs,” Journal of Pharmaceutical Sciences, 1975, vol. 64 (3), pp. 367-391.
Brickner, S.J. et al., “Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections,” Journal of Medicinal Chemistry, 1996, vol. 39 (3), pp. 673-679.
Bruzzone S., et al., “Catastrophic NAD+ Depletion in Activated T Lymphocytes through Nampt Inhibition Reduces Demyelination and Disability in EAE,” PLoS One, 2009, vol. 4 (11), pp. e7897.
Busso N., et al., “Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase/visfatin Enzymatic Activity Identifies a New Inflammatory Pathway Linked to NAD,” PLoS One, 2008, vol. 3 (5), pp. e2267.
Czajka, D. M. et al., “Effect of Deuterium Oxide on the Reproductive Potential of Mice,” Annals of the New York Academy of Sciences, 1960, vol. 84, pp. 770-779.
Czajka, D. M. et al., “Physiological Effects of Deuterium on Dogs,” American Journal of Physiology, 1961, vol. 201 (2), pp. 357-362.
Foster, A. B. et al., “Deuterium Isotope Effects in the Metabolism of Drugs and Xenobiotics: Implications for Drug Design,” Advances in Drug Research, 1985, vol. 14, pp. 2-36.
Galli M., et al., “The Nicotinamide Phosphoribosyltransferase: A Molecular Link Between Metabolism, Inflammation, and Cancer,” Cancer Research, 2010, vol. 70 (1), pp. 8-11.
Garten A., et al., “Nampt: Linking NAD Biology, Metabolism and Cancer,” Trends in Endocrinology and Metabolism, 2009, vol. 20 (3), pp. 130-138.
Hansen C.M., et al., “Cyanoguanidine CHS 828 Induces Programmed Cell Death with Apoptotic Features in Human Breast Cancer Cells in Vitro,” Anticancer Research, 2000, vol. 20 (6B), pp. 4211-4220.
Kato, S. et al., “Synthesis of Deuterated Mosapride Citrate,” Journal of Labelled Compounds and Radiopharmaceuticals, 1995, vol. 36 (10), pp. 927-932.
Kim S.R., et al., “Visfatin Promotes Angiogenesis by Activation of Extracellular Signal-regulated Kinase 1/2,” Biochemical and Biophysical Research Communications, 2007, vol. 357 (1), pp. 150-156.
Kushner, et al., “Pharmacological uses and perspectives of heavy water and deuterated compounds,” Canadian Journal of Physiology and Pharmacology, 1999, vol. 77 (2), pp. 79-88.
Lizondo, J. et al., “Linezolid: Oxazolidinone antibacterial,” Drugs of the Future, 1996, vol. 21 (11), pp. 1116-1123.
Mallesham, B. et al., “Highly Efficient Cul-Catalyzed Coupling of Aryl Bromides With Oxazolidinones Using Buchwald's Protocol: A Short Route to Linezolid and Toloxatone,” Organic Letters, 2003, vol. 5 (7), pp. 963-965.
Olesen U.H., et al., “A Preclinical Study on the Rescue of Normal Tissue by Nicotinic Acid in High-dose Treatment with APO866, a Specific Nicotinamide Phosphoribosyltransferase Inhibitor,” Molecular Cancer Therapeutics, 2010, vol. 9 (6), pp. 1609-1617.
Partial International Search Report for Application No. PCT/US2013/040476 mailed date Jul. 12, 2013, 3 pages.
Thomson, J.F., “Physiological Effects of D20 in Mammals,” Annals of the New York Academy of Sciences, 1960, vol. 84, pp. 736-744.
Van Beijnum J.R., et al., “Target Validation for Genomics Using Peptide-specific Phage Antibodies: A Study of Five Gene Products Overexpressed in Colorectal Cancer,” International Journal of Cancer, 2002, vol. 101 (2), pp. 118-127.
Ziegler M., “New Functions of a Long-known Molecule. Emerging Roles of NAD in Cellular Signaling,” European Journal of Biochemistry, 2000, vol. 267 (6), pp. 1550-1564.
International Search Report for Application No. PCT/US2013/040476, mailed on Oct. 15, 2013, 5 pages.
Related Publications (1)
Number Date Country
20130303511 A1 Nov 2013 US
Provisional Applications (3)
Number Date Country
61779626 Mar 2013 US
61718998 Oct 2012 US
61645679 May 2012 US