Claims
- 1. A compound of formula (I):
- 2. A compound of claim 1, wherein the compound is of formula (I):
- 3. The compound of claim 2, wherein
m is 0.
- 4. The compound of claim 3, wherein: ring B is selected from
- 5. The compounds of claim 4, wherein:
R5, at each occurrence, is independently selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CRR)rOH, (CRR)rSH, (CRR)rOR5d, (CRR)rSR5d, (CRR)rNR5aR5a, (CRR)rC(O)OH, (CRR)rC(O)R5b, (CRR)rC(O)NR5aR5a, (CRR)rNR5aC(O)R5b, (CRR)rNR5aC(O)OR5d, (CRR)rOC(O)NR5aR5a, (CHR)rNR5aC (O)NR5aR5a, CRR(CRR)rNR5aC(O)H, (CRR)rC(O)OR5b, (CRR)rOC(O)R5b, (CRR)rS(O)pR5b, (CRR)rS(O)2NR5aR5a, (CRR)rNR5aS(O)2R5b, and C1-6 haloalkyl; R5a, at each occurrence, is independently selected from H, methyl, C1-6 alkyl substituted with 0-2 R5e wherein the alkyl is selected from ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, hexyl, C3 alkenyl substituted with 0-1 R5e, wherein the alkenyl is selected from allyl, C3 alkynyl substituted with 0-1 R5e wherein the alkynyl is selected from propynyl, and a (CH2)r—C3-4 carbocyclic residue substituted with 0-5 R5e, wherein the carbocyclic residue is selected from cyclopropyl, and cyclobutyl; R5b, at each occurrence, is selected from C1-6 alkyl substituted with 0-2 R5e, wherein the alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, and hexyl, a (CH2)r—C3-4 carbocyclic residue substituted with 0-2 R5e, wherein the carbocyclic residue is selected from cyclopropyl, and cyclobutyl; and R5d, at each occurrence, is selected from methyl, CF3, C2-6 alkyl substituted with 0-2 R5e, wherein the alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, and hexyl, C3-8 alkenyl, C3-8 alkynyl, and a C3-10 carbocyclic residue substituted with 0-3 R5e.
- 6. The compound of claim 5, wherein:
R4 is selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, (CRR)tOH, (CRR)tSH, (CRR)tOR4d, (CRR)tSR4d, (CRR)tNR4aR4a, (CRR)qC(O)OH, (CRR)rC(O)R4b, (CRR)rC(O)NR4aR4a, (CRR)tNR4aC(O)R4b, (CRR)tOC(O)NR4aR4a, (CRR)tNR4aC(O)OR4d, (CRR)tNR4aC(O)R4b, (CRR)rC(O)OR4b, (CRR)tOC(O)R4b, (CRR)rS(O)pR4b, (CRR)rS(O)2NR4aR4a, (CRR)rNR4aS(O)2R4b; R, at each occurrence, is independently selected from H, methyl, ethyl, propyl, allyl, propynyl, (CH2)rC3-6 cycloalkyl, and (CH2)rphenyl substituted with R6e; R5, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, allyl, propynyl, (CH2)rOH, (CH2)rOR5d, (CH2)rNR5aR5a, (CH2)rC(O)OH, (CH2)rC(O)R5b, (CH2)rC(O)NR5aR5a, (CH2)rNR5aC(O)R5b, (CH2)rOC(O)NR5aR5a, (CH2)rNR5aC(O)OR5d, (CH2)rNR5aC(O)R5b, (CH2)rC(O)OR5b, (CH2)rOC(O)R5b, (CH2)rNR5aS(O)2R5b, and C1-6 haloalkyl; R5a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, hexyl, cyclopropyl, and cyclobutyl; and r, at each occurrence, is selected from 0, 1, and 2.
- 7. The compound of claim 6, wherein:
R1 is selected from phenyl substituted with 0-2 R6, naphthyl substituted with 0-2 R6, and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R6 wherein the heteroaryl is selected from indolyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzoxazolyl, benzthiazolyl, benzo[b]thiophene, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrido[2,3-d]pyrimidinyl, pyrimido[5,4-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, pyridinyl, pyrimidinyl, pyrrolyl, pyrrolo[2,1-f][1,2,4]triazine, quinazolinyl, quinolinyl, thiazolyl, thienyl, and tetrazolyl; R2 is selected from phenyl substituted with 0-2 R7, and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R7 wherein the heteroaryl is selected from indolyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzoxazolyl, benzthiazolyl, benzo[b]thiophene, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinyl isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrido[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, pyridinyl, pyrimidinyl, pyrrolyl, pyrrolo[2,1-f][1,2,4]triazine, quinazolinyl, quinolinyl, thiazolyl, thienyl, and tetrazolyl; R4 is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, allyl, propynyl, (CRR)qOH, (CRR)tSH, (CRR)tOR4d, (CRR)tSR4d, (CRR)tNR4aR4a, (CRR)qC(O)OH, (CRR)rC(O)R4b, (CRR)rC(O)NR4aR4a, (CRR)tNR4aC(O)R4b, (CRR)tOC(O)NR4aR4a, (CRR)tNR4aC(O)OR4d, (CRR)tNR4aC(O)R4b, (CRR)rC(O)OR4b, (CRR)tOC(O)R4b, (CRR)rS(O)pR4b, (CRR)rS(O)2NR4aR4a, (CRR)rNR4aS(O)2R4b; R4a, at each occurrence, is independently selected from H, methyl substituted with 0-1 R4c, C2-6 alkyl substituted with 0-3 R4e wherein C2-6 is selected from ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl and hexyl, and a (CH2)r—C3-6 carbocyclic residue substituted with 0-4 R4e wherein the carbocyclic residue is selected from cyclopropyl, cyclohexyl, and phenyl; R4b is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and cyclopropyl; R4d is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and cyclopropyl; and R8 is selected from H, methyl, ethyl, propyl, i-propyl, and cyclopropyl.
- 8. The compound of claim 7, wherein:
R6, at each occurrence, is selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CR′R′)rC3-6 cycloalkyl, Cl, Br, I, F, NO2, CN, (CR′R′)rNR6aR6a, (CR′R′)rOH, (CR′R′)rO(CR′R′)rR6d, (CR′R′)rSH, (CR′R′)rC(O)H, (CR′R′)rS(CR′R′)rR6d, (CR′R′)rC(O)OH, (CR′R′)rC(O)(CR′R′)rR6b, (CR′R′)rC(O)NR6aR6a, (CR′R′)rNR6fC(O)(CR′R′)rR6b, (CR′R′)rC(O)O(CR′R′)rR6d, (CR′R′)rNR6aC(O)NR6aR6a, (CR′R′)rNR6aC(S)NR6aR6a, (CR′R′)rOC(O)(CR′R′)rR6b, (CR′R′)rS(O)p(CR′R′)rR6b, (CR′R′)rS(O)2NR6aR6a, (CR′R′)rNR6fS(O)2(CR′R′)rR6b, (CR′R′)rNR6fS(O)2NR6aR6a, C1-6 haloalkyl, and (CR′R′)rphenyl substituted with 0-3 R6e, and a (CH2)r-5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R6e; R6a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl and phenyl; R6b, at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl; R6d, at each occurrence, is selected from methyl, CF3, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl; R6e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR6fR6f, and (CH2)rphenyl; R6f, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl; R7 is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, t-butyl, pentyl, hexyl, (CR′R′)rC3-6 cycloalkyl, Cl, Br, I, F, NO2, CN, (CR′R′)rNR7aR7a, (CR′R′)rOH, (CR′R′)rO(CH)rR7d, (CR′R′)rSH, (CR′R′)rC(O)H, (CR′R′)rS(CR′R′)rR7d, (CR′R′)rC(O)OH, (CR′R′)rC()(CR′R′)rR7b, (CR′R′)rC(O)NR7aR7a, (CR′R′)rNR7fC(O)(CR′R′)rR7b, (CR′R′)rC(O)O(CR′R′)rR7d, (CR′R′)rOC(O)(CR′R′)rR7b, (CR′R′)rNR7aC(O)NR7aR7a, (CR′R′)rNR7aC(O)O(CR′R′)rR7d, (CR′R′)rS(O)p(CR′R′)rR7b, (CR′R′)rS(O)2NR7aR7a, (CR′R′)rNR7fS(O)2(CR′R′)rR7b, C1-6 haloalkyl, and (CR′R′)rphenyl substituted with 0-3 R7e; R7a, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl,, prop-2-enyl, 2-methyl-2-propenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH2cyclopropyl, and benzyl; R7b, at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, CH2-cyclopentyl, cyclohexyl, CH2-cyclohexyl, CF3, pyrrolidinyl, morpholinyl, piperizenyl substituted with 0-1 R7e, and azetidinyl; R7d, at each occurrence, is selected from methyl, CF3, CF2CF3, CHF2, CH2F, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, and cyclopropyl; R7e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, C(O)OC1-5 alkyl, (CH2)rSC1-5 alkyl, (CH2)rNR7fR7f, and (CH2)rphenyl; R7f, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, and phenyl; and r is 0 or 1.
- 9. The compound of claim 8, wherein:
R7 is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, pentyl, hexyl, Cl, Br, I, F, CN, NO2, NR7aR7a, NHC(O)NHR7a, NR7aC(O)R7b, NR7aC(O)OR7d, CF3, CF2CF3, CHF2, CH2F, OCF3, C (O) R7b, C(O)OR7d, NR7fC(O)NR7aR7a, NHS(O)2R7b, 144
- 10. The compound of claim 9, wherein:
ring B is selected from 145ring B being optionally substituted with 0-1 R5; Z is selected from a bond, —NR8C(O)—, —C(O)NH—, and —NHC(O)NH—; R1 is selected from a C6-10 aryl group substituted with 0-3 R6 wherein the aryl group is selected from phenyl and naphthyl, and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N and O, substituted with 0-3 R6 wherein the heteroaryl system is selected from indolyl, pyridinyl, pyrimidinyl, pyrido[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, imidazyolyl, and pyrrolyl R2 is phenyl substituted with 0-2 R7; R4 is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, and (CH2)rC(O)R4b; R6 is selected from methyl, ethyl, propyl, i-propyl, butyl, F, Cl, Br, I, NO2, CN, O(CH2)rR6d, C(O)H, C(O)R6d, C(O)OH, SR6d, NR6aR6a, NC(O)R6b, OC(O)R6b, S(O)pR6b, (CHR′)rS(O)2NR6aR6a, and CF3; R6a is H, methyl, or ethyl; R6b is H, methyl, ethyl, propyl, i-propyl or butyl; R6d is methyl, phenyl, CF3, and (CH2)-phenyl; and r is 0 or 1.
- 11. The compound of claim 10, wherein:
ring B is selected from 146ring B being substituted with 0-1 R5; R1 is selected from a C6-10 aryl group substituted with 0-3 R6 wherein the aryl group is selected from phenyl, and a 5-10 membered heteroaryl system containing 1-4 heteroatoms selected from N and O, substituted with 0-3 R6 wherein the heteroaryl system is selected from indolyl and pyridinyl; R4 is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, allyl and (CH2)rC(O)R4b; R5 is selected from H, OH, OCH3, and NR5aR5a; R5a is selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, hexyl, allyl, propargyl, cyclopropyl, cyclopropylmethyl, acetyl, methysulfonyl, —C(O)CF3, C(═N)NH2, benzyl, and —C(O)O-t-butyl; R6 is selected from methyl, ethyl, propyl, i-propyl, butyl, vinyl, F, Cl, Br, I, CN, NR6aR6a, C(O)H, C(O)OH, C(O)R6b, SR6d, S(O)pR6d, S(O)2NR6aR6a, CF3, and CH2OH; R6b is H, methyl, ethyl, propyl, i-propyl or butyl; R6d is methyl; R7 is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, pentyl, hexyl, Cl, Br, I, F, CN, NO2, NR7aR7a, NHC(O)NHR7a, NR7aC(O)R7b, NR7aC(O)OR7d, CF3, CF2CF3, CHF2, CH2F, OCF3, OCF2CF3, OCHF2, and OCH2F, C(O)OR7d, C(O)R7b, NR7fC(O)NR7aR7a, NHS(O)2R7b, 147R7a is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; R7b is selected from cyclohexyl and CF3; and R7d is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, and t-butyl.
- 12. The compound of claim 11, wherein:
ring B is selected from 148ring B being substituted with 0-1 R5; R1 is selected from a C6-10 aryl group substituted with 0-3 R6 wherein the aryl group is phenyl; R6 is selected from methyl, ethyl, propyl, i-propyl, F, Cl, Br, CN, SCH3, and CF3; R7 is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, s-butyl, t-butyl, pentyl, hexyl, phenyl, adamantyl, benzyl, Cl, Br, I, F, CN, NO2, NR7aR7a, OR7d, NHC(O)NHR7a, NR7aC(O)R7b, NR7aC(O)OR7d, CF3, CF2CF3, CHF2, CH2F, OCF3, OCF2CF3, OCHF2, and OCH2F, C(O)OR7d, C(O)R7b, and NR7fC(O)NR7aR7a; R7a is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
- 13. The compound of claim 12, wherein
E is selected from —CH2—NH—, —C(O)—NH— and —SO2—CH2—.
- 14. The compound of claim 1, wherein
B is 149ring B being substituted with 0-1 R5; and R5 is selected from H, N(→O)R5aR5a, N3, NR5aC(O)R5b, NR5aC(O)H, NR5aC(O)OR5d, NR5aC(O)NR5aR5a, and NR5aR5a, and a (CH2)r-5-6 membered heterocyclic system containing 1-2 heteroatoms selected from N, O, and S, substituted with 0-2 R5e, wherein the heterocyclic system is selected from pyrrolidinyl, piperidinyl, pyrrolidin-2-one, and isothiazolidine 1,1-dioxide.
- 15. The compound of claim 12, wherein
Z is selected from a bond, —NR8C(O)—, —C(O)NH—, and —NHC(O)NH—.
- 16. The compound of claim 12, wherein
R6 is selected from methyl, ethyl, propyl, i-propyl, butyl, vinyl, F, Cl, Br, I, C(O)H, C(O)R6b, SR6d, S(O)pR6d, CF3, and CH2OH; R6b is H, methyl, ethyl, propyl, i-propyl or butyl; R6d is methyl; R7 is selected from Cl, Br, NR7aR7a, NR7aC(O)OR7d, NHC(O)NHR7a, OCF3, and CF3; R7a is selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; R7d is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, and t-butyl.
- 17. The compound of claim 1, wherein the compound is of formula (Ia) or (Ic)
- 18. The compound of claim 1, wherein the compound is of formula (I) is selected:
2-{(3S)-1-[(1,2-cis)-2-(4-Methylsulfanyl-benzoylamino)-cyclohexyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester; 2-{(3S)-1-[(1,2-cis)2-(4-Methylsulfanyl-benzoylamino)-cyclohexyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-amino; N-{(3S)-1-[(1S,2R,4R)-(Isopropyl-methyl-amino)-2-(toluene-4-sulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4S)-(Isopropyl-methyl-amino)-2-(toluene-4-sulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4S)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-ethyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4S)-2-Benzenesulfonylmethyl-4-(isopropyl-ethyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-cyclopropylmethyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-Azido-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) N-(3S*)-1-[(1S*,2R*,4R*)-4-Amino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) N-{(3S*)-1-[(1S*,2R*,4R*)-4-(Isopropyl-prop-2-ynyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) N-(3S*)-1-[(1S*,2R*,4R*)-4-(Cyclopropylmethyl-isopropyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-3-methyl-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-N-methyl-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; 1-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-(3-trifluoromethyl-phenyl)-urea; N-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzenesulfonamide; N-{(3S)-1-[(1S,2R,4R)-4-(Isopropyl-methyl-amino)-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-benzamide; {(3S)-1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-(3-trifluoromethyl-phenyl)-urea; N-[(3S)-1-((1S,2R,4R)-2-Benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-2-oxo-pyrrolidin-3-yl]-3-trifluoromethyl-benzamide; N-{(3S)-1-[(1S,2R,4R)-4-(Allyl-isopropyl-amino)-2-benzenesulfonylmethyl-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; 1-((1S,2R)-2-Benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-2-oxo-pyrrolidine-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide; 1-((1S,2R)-2-Benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-2-oxo-pyrrolidine-3-carboxylic acid (3-trifluoromethyl-phenyl)-amide; (2-{(3S)-1-[(1S,2R)-2-(4-Methylsulfanyl-benzylamino)-cyclohexyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester; N-{(3S)-1-((1S,2R,4R)-2-Benzenesulfonylmethyl-4(R)-(isopropyl-propyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; (±) 1-[(1S,2R*,4R*)-4-Isopropylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one; (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one; (±) 1-[(1S*,2R*,4R*)-4-Isopropylmethylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one; (±) 1-[(1S*,2R*,4R*)-4-Amino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethoxyphenyl)-5,6-dihydro-1H-pyridin-2-one; (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethoxyphenyl)-5,6-dihydro-1H-pyridin-2-one; (±) 1-[(1S*,2R*,4R*)-4-Isopropylamino-2-(4-benzenesulfonylmethyl)-cyclohexyl]-4-(3-trifluoromethyl-phenyl)-piperidin-2-one; (S)-3-(3-(trifluoromethyl)benzylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-((4-(methylthio)phenylsulfonyl)methyl)cyclohexyl)pyrrolidin-2-one; 3(R)-(3-(trifluoromethyl)phenethyl)-1-((1S,2R,4R/S)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one trifluoroacetate 3(S)-(3-(Trifluoromethyl)phenethyl)-1-((1S,2R,4R/S)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one trifluoroacetate N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxoazepan-3-yl)-3-(trifluoromethyl)benzamide; N-((S)-1-((1S,2R,4R)-4-(dimethylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopiperidin-3-yl)-3-(trifluoromethyl)benzamide; (R*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one; (S*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one; (S*)-3-(2-oxo-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (R*)-3-(2-oxo-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (R*)-3-(2-hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (S*)-3-(2-hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; ((S*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(-2-(methoxyimino)-2-(3-(trifluoromethyl)phenyl)ethyl)pyrrolidin-2-one; ((R*)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(-2-(methoxyimino)-2-(3-(trifluoromethyl)phenyl)ethyl)pyrrolidin-2-one; 1-((1S*,2R*,4R*)-4-(amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one; 1-((1S*,2R*,4R*)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one; 1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one; 1-((1S*,2R*,4R*)-4-(isopropyl(ethyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one; 1-((1S*,2R*,4R*)-4-(Diethylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one; 1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(naphthalen-1-ylamino)pyrrolidin-2-one; 3-(Benzo[b]thiophen-3-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (S)-3-(6-chloroquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (S)-3-(6,8-dichloroquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; 3,5-Dichloro-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethoxy)benzamide; 3-((E)-3(R*)-(trifluoromethyl)styryl)-1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; 1-((1S*,2R*,4R*)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3(R*)-((E/Z)-2-(3-(trifluoromethyl)phenyl)prop-1-enyl)pyrrolidin-2-one; N-(1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3(R)-yl)benzamidede; N-((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3,5-bis(trifluoromethyl)benzamide; 2-Amino-N-(1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3(R)-yl)-5-(trifluoromethoxy)benzamide; (R)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(6-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one; (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(6-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one; (R)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one; (S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(7-(trifluoromethyl)quinolin-4-ylamino)pyrrolidin-2-one; 3-(2-(Phenyl)phenylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; 3-(3,5-Bis(trifluoromethyl)phenylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; 1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(2-(trifluoromethyl)phenylamino)pyrrolidin-2-one; 1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(2-methoxyphenylamino)pyrrolidin-2-one; 1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(3-(trifluoromethyl)phenylamino)pyrrolidin-2-one; 1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(4-(trifluoromethyl)phenylamino)pyrrolidin-2-one; 3-Chloro-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; 3-Fluoro-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethyl)benzamide; tert-Butyl(1R,3R,4S)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexylcarbamate; N-((S)-2-Oxo-1-((1S,2R,4R)-4-(phenylamino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; N-(2-Oxo-1-((1S,2R,4R)-2-(phenylsulfonylmethyl)-4-(pyridin-4-ylamino)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; N-(2-Oxo-1-((1S,2R,4R)-2-(phenylsulfonylmethyl)-4-(thiazol-2-ylamino)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; Methyl (1R,3R,4S)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexylcarbamate; N-((S)-1-((1S,2R,4R)-4-Formamido-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; 1-((1R,3R,4S)-4-((S)-2-Oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexyl)urea; 1-Methyl-3-((1R,3R,4S)-4-((S)-2-oxo-3-(3-(trifluoromethyl)benzamido)pyrrolidin-1-yl)-3-(phenylsulfonylmethyl)cyclohexyl)urea; N-((S)-2-Oxo-1-((1S,2R,4R)-4-(2-oxopyrrolidin-1-yl)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; N-((S)-1-((1S,2R,4R)-4-(1,1-dioxido-isothiazolidin-2-yl)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; N-((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-fluoro-5-(trifluoromethyl)benzamide; 3-Chloro-N-((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; N-((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3,5-bis(trifluoromethyl)benzamide; tert-Butyl 2-(((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)carbamoyl)-4-(trifluoromethoxy)phenylcarbamate; 2-Amino-N-((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethoxy)benzamide; N-((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethoxy)benzamide; N-((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; 3,5-Dichloro-N-((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; 3-Chloro-N-((S)-1-((1S,2R,4R)-2-((4-chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide N-Oxide; N-((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide N-Oxide; N-((S)-1-((1S,2R,4R)-2-((4-Chlorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-fluoro-5-(trifluoromethyl)benzamide N-Oxide; N-((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide N-Oxide; N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-((4-isopropylphenylsulfonyl)methyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(o-tolylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; N-((S)-1-((1S,2R,4R)-2-((4-Fluorophenylsulfonyl)methyl)-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide; 3-Chloro-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(tosylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; 2-Amino-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(tosylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethoxy)benzamidemide; 1-[(1S,2R,4R)-(4-Amino-2-benzenesulfonyl-methylcyclohexyl)-4-(3-trifluoromethylphenyl)]-5,6-dihydro-1H-pyridin-2-one; 1-([(1S,2R,4R)-2-benzenesulfonylmethyl-4-isopropylamino-cyclohexyl)-4-(3-trifluoromethylphenyl)-5,6-dihydro-1H-pyridin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-ethyl-amino)cyclohexyl]-4-(3-trifluoromethyl-phenyl)-5,6-dihydro-1H-pyridin-2-one; 1-[1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-trifluoromethyl-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(7-chloro-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(2,6-dichloro-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-dimethylamino-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-hydroxy-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-trifluoromethyl-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-thieno[3,2-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-2-trifluoromethyl-thieno[3,2-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-pyrrolidin-2-one; (3S)-3-(6-Adamantan-1-yl-pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-pyrrolidin-2-one; 3-Methyl-2-phenyl-3H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; 1-Methyl-2-phenyl-1H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; 3-Benzyl-2-phenyl-3H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; 1-Benzyl-2-phenyl-1H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; 2-Phenyl-3H-imidazole-4-carboxylic acid {(3S)-1-[(1S,2R, 4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; Preparation of 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6,7-dimethoxy-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-fluoro-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-methyl-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-propyl-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-isopropyl-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(2-tert-butyl-6-chloro-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-methyl-quinazolin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-ethyl-quinazolin-4-ylamino)-pyrrolidin-2-one; N-{(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2,5-dioxo-pyrrolidin-3-yl}-3-trifluoromethyl-benzamide; N-{(3S)-1-[-(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-4-adamantan-1-yl-1H-pyrrole-2-carboxamide; N-{(3S)-1-[-(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-4-adamantan-1-yl-1-methyl-1H-pyrrole-2-carboxamide; 1-[(1S,2R,4R)-2-Benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-tert-butyl-pyrimido[5,4-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 5-Bromo-2-tert-butyl-pyrimidine-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; 2-tert-Butyl-pyrimidine-4-carboxylic acid {(3S*)-1-[(1S*,2R′,4R )-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; 2-tert-Butyl-5-phenyl-pyrimidine-4-carboxylic acid {(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-amide; N-{(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-tert-butyl-benzamide; N-{(3S)-1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-3-bromo-5-tert-butyl-benzamide; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-trifluoromethyl-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-trifluoromethoxy-pyrido[2,3-d]pyrimidin-4-ylamino)-pyrrolidin-2-one; 1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-(3S)-3-(6-chloro-2-methylamino-quinazolin-4-ylamino)-pyrrolidin-2-one; (3S)-3-(6-Fluoro-quinazolin-4-ylamino)-1-[(1S,2R,4R)-4-(isopropyl-methyl-amino)-2-(toluene-4-sulfonylmethyl)-cyclohexyl]-pyrrolidin-2-one; N-{1-[(1S,2R,4R)-2-benzenesulfonylmethyl-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-(3S)-3-yl}-2-chloro-5-trifluoromethyl-benzamide; (S)-3-(6-Bromoquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (S)-3-(6,7-Difluoroquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; (S)-3-(6-Methoxyquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; ((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-(quinazolin-4-ylamino)pyrrolidin-2-one; 3-Phenyl-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; (S)-3-(6-Iodoquinazolin-4-ylamino)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)pyrrolidin-2-one; 3-Tert-butyl-4-hydroxy-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)benzamide; 3-Amino-5-tert-butyl-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)thiophene-2-carboxamide; N-((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-2-methyl-5-phenylfuran-3-carboxamide; N-((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-nitrofuran-2-carboxamide; and N-((S)-1-((1S,2R,4R)-4-(Isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-4-phenylthiophene-2-carboxamide.
- 19. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1.
- 20. A method for modulation of chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.
- 21. A method for modulation of MCP-1, MCP-2, MCP-3 and MCP-4, and MCP-5 activity that is mediated by the CCR2 receptor comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.
- 22. A method for modulation of MCP-1 activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.
- 23. A method for treating disorders, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, said disorders being selected from osteoarthritis, aneurism, fever, cardiovascular effects, Crohn's disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis, restinosis, organ transplantation, and cancer.
- 24. The method for treating disorders, of claim 23, wherein said disorders being selected from psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis restinosis, organ transplantation, and cancer.
- 25. The method for treating disorders, of claim 24, wherein said disorders being selected from alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis restinosis, organ transplantation, and cancer.
- 26. The method for treating disorders, of claim 25, wherein said disorders being selected from asthma, multiple sclerosis, artherosclerosis, and rheumatoid arthritis.
- 27. A method for treating inflammatory diseases, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.
- 28. A method for modulation of CCR2 activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.
- 29. The method for treating disorders, of claim 25, wherein said disorders being selected from restinosis, organ transplantation, and cancer.
- 30. A compound of Formula (II)
- 31. The compound of claim 30, wherein
W is selected from H, I, and Br; and Pg, at each occurrence, is independently selected from benzyloxycarbonyl (Cbz) and tert-butyloxycarbonyl (Boc).
- 32. A process for preparing a compound of Formula (Ia)
- 33. A process for preparing a compound of Formula (II)
- 34. The process of claim 33 wherein
the electrophile is selected from iodine, bromine, N-bromo-succimide, and N-iodosuccinimide; and the base is selected from n-butyl lithium, lithium diisopropylamide (LDA), sodium hydride, lithium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)-amide, and Li—Al(O-tButyl)4.
- 35. A process for preparing a compound of Formula (IIa)
- 36. The process of claim 35, wherein the reducing agent is selected from tris-(trimethylsilyl)silane, zinc metal, tributyltin hydride and AIBN.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the priority benefits of U.S. Provisional Application No. 60/446,850, filed Feb. 12, 2003, which is expressly incorporated fully herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60446850 |
Feb 2003 |
US |