Claims
- 1. A compound of Formula I
- 2. A compound of claim 1 wherein
R1 is selected from hydrido, lower alkyl, lower cycloalkyl, lower alkenyl, lower alkynyl, lower heterocyclyl, lower cycloalkylalkylene, lower haloalkyl, lower hydroxyalkyl, lower aralkyl, lower alkoxyalkyl, lower mercaptoalkyl, lower alkylthioalkylene, amino, lower alkylamino, lower arylamino, lower alkylaminoalkylene, and lower heterocyclylalkylene; or R1 has the formula 5896wherein:
i is 0, 1 or 2; and R25 is selected from hydrogen, lower alkyl, lower phenylalkyl, lower heterocyclylalkyl, lower alkoxyalkylene, lower phenoxyalkylene, lower aminoalkyl, lower alkylaminoalkyl, lower phenoxyaminoalkyl, lower alkylcarbonylalkylene, lower phenoxycarbonylalkylene, and lower heterocyclylcarbonylaminoalkylene; and R26 is selected from hydrogen, lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkylalkylene, lower phenylalkyl, lower alkoxycarbonylalkylene, and lower alkylaminoalkyl; and R27 is selected from lower alkyl, lower cycloalkyl, lower alkynyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower phenylalkyl, lower cycloalkylalkylene, lower cycloalkenylalkylene, lower cycloalkylarylene, lower cycloalkylcycloalkyl, lower heterocyclylalkylene, lower alkylphenylene, lower alkylphenylalkyl, lower phenylalkylphenylene, lower alkylheterocyclyl, lower alkylheterocyclylalkylene, lower alkylheterocyclylphenylene, lower phenylalkylheterocyclyl, lower alkoxyalkylene, lower alkoxyphenylene, lower alkoxyphenylalkyl, lower alkoxyheterocyclyl, lower alkoxyalkoxyphenylene, lower phenoxyphenylene, lower phenylalkoxyphenylene, lower alkoxyheterocyclylalkylene, lower phenoxyalkoxyphenylene, lower alkoxycarbonylalkylene, lower alkoxycarbonylheterocyclyl, lower alkoxycarbonylheterocyclylcarbonylalkylene, lower aminoalkyl, lower alkylaminoalkylene, lower phenylaminocarbonylalkylene, lower alkoxyphenylaminocarbonylalkylene, lower aminocarbonylalkylene, arylaminocarbonylalkylene, lower alkylaminocarbonylalkylene, lower phenylcarbonylalkylene, lower alkoxycarbonylphenylene, lower phenoxycarbonylphenylene, lower alkylphenoxycarbonylphenylene, lower phenylcarbonylphenylene, lower alkylphenylcarbonylphenylene, lower alkoxycarbonylheterocyclylphenylene, lower alkoxycarbonylalkoxylphenylene, lower heterocyclylcarbonylalkylphenylene, lower alkylthioalkylene, cycloalkylthioalkylene, lower alkylthiophenylene, lower phenylalkylthiophenylene, lower heterocyclylthiophenylene, lower phenylthioalklylphenylene, lower phenylsulfonylaminoalkylene, lower alkylsulfonylphenylene, lower alkylaminosulfonylphenylene; wherein said lower alkyl, lower cycloalkyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower phenylalkyl, lower heterocyclylalkylene, lower alkylheterocyclylphenylene, lower alkoxyphenylene, lower phenoxyphenylene, lower phenylaminocarbonylalkylene, lower phenoxycarbonylphenylene, lower phenylcarbonylphenylene, lower alkylthiophenylene, lower heterocyclylthiophenylene, lower phenylthioalklylphenylene, and lower alkylsulfonylphenylene groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, lower haloalkyl, lower alkoxy, keto, amino, nitro, and cyano; or R27 is —CHR46R47 wherein R46 is lower alkoxycarbonyl, and R47 is selected from lower phenylalkyl, lower phenylalkoxyalkylene, lower heterocyclylalkylene, lower alkylheterocyclylalkylene, lower alkoxycarbonylalkylene, lower alkylthioalkylene, and lower phenylalkylthioalkylene; wherein said phenylalkyl and heterocylcyl groups are optionally substituted with one or more radicals independently selected from lower alkyl and nitro; or R26 and R27 together with the nitrogen atom to which they are attached form a 4-8 membered ring heterocycle, wherein said heterocycle is optionally substituted with one or more radicals independently selected from lower alkyl, aryl selected from phenyl, biphenyl and naphthyl, heterocyclyl, heterocyclylalkylene, lower alkylheterocyclylalkylene, lower phenoxyalkylene, lower alkoxyphenylene, lower alkylphenoxyalkylene, lower alkylcarbonyl, lower alkoxycarbonyl, lower phenylalkoxycarbonyl, lower alkylamino and lower alkoxycarbonylamino; wherein said aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclylalkylene and lower phenoxyalkylene radicals are optionally substituted with one or more radicals independently selected from halogen, lower alkyl and lower alkoxy; and R2 is selected from hydrido, halogen, lower alkyl, aryl selected from phenyl, biphenyl, and naphthyl, lower haloalkyl, lower hydroxyalkyl, 5- or 6-membered heterocyclyl, lower alkylheterocyclyl, lower heterocyclylalkyl, lower alkylamino, lower alkynylamino, phenylamino, lower heterocyclylamino, lower heterocyclylalkylamino, lower phenylalkylamino, lower aminoalkyl, lower aminoalkylamino, lower alkylaminoalkylamino, lower cycloalkyl, lower alkenyl, lower alkoxycarbonylalkyl, lower cycloalkenyl, lower carboxyalkylamino, lower alkoxycarbonyl, lower heterocyclylcarbonyl, lower alkoxycarbonylheterocyclyl, lower alkoxycarbonylheterocyclylcarbonyl, alkoxycarbonylalkyl, lower alkoxyalkylamino, lower alkoxycarbonylaminoalkylamino, lower heterocyclylsulfonyl, lower heterocyclyloxy, and lower heterocyclylthio; wherein the aryl, heterocylyl, heterocyclylalkyl, cycloalkyl, and cycloalkenyl groups are optionally substituted with one or more radicals independently selected from halo, keto, lower alkyl, lower alkynyl, phenyl, 5- or 6-membered heterocyclyl, lower phenylalkyl, lower heterocyclylalkyl, lower epoxyalkyl, carboxy, lower alkoxy, lower aryloxy, lower phenylalkoxy, lower haloalkyl, lower alkylamino, lower alkylaminoalkylamino, lower alkynylamino, lower amino(hydroxyalkyl), lower heterocyclylalkylamino, lower alkylcarbonyl, lower alkoxycarbonyl, lower alkylsulfonyl, lower phenylalkylsulfonyl, and phenylsulfonyl; or R2 has the formula: 5897wherein:
j is 0, 1 or 2; and m is 0; R30 and R31 are independently selected from hydrogen, alkyl, aryl, heterocyclyl, aralkyl, heterocyclylalkylene, aminoalkyl, alkylaminoalkyl, aminocarbonylalkyl, alkoxyalkyl, and alkylcarbonyloxyalkyl; and R32 is selected from hydrogen, alkyl, aralkyl, heterocyclylalkyl, alkoxyalkylene, aryloxyalkylene, aminoalkyl, alkylaminoalkyl, arylaminoalkyl, alkylcarbonylalkylene, arylcarbonylalkylene, and heterocyclylcarbonylaminoalkylene; and R33 is selected from hydrogen, alkyl, —C(O)R35, —C(O)OR35, —SO2R36, —C(O)NR37R38, and —SO2NR39R40; wherein R35 is selected from alkyl, cycloalkyl, haloalkyl, alkenyl, aryl, heterocyclyl, aralkyl, arylcycloalkyl, cycloalkenylalkylene, heterocyclylalkylene, alkylarylene, alkylheterocyclyl, arylarylene, arylheterocyclyl, alkoxy, alkenoxy, alkoxyalkylene, alkoxyaralkyl, alkoxyarylene, aryloxyalkylene, aralkoxyalkylene, cycloalkyloxyalkylene, alkoxycarbonyl, heterocyclylcarbonyl, alkylcarbonyloxyalkylene, alkylcarbonyloxyarylene, alkoxycarbonylalkylene, alkoxycarbonylarylene, aralkoxycarbonylheterocyclyl, alkylcarbonylheterocyclyl, arylcarbonyloxyalkylarylene, and alkylthioalkylene; wherein said aryl, heterocyclyl, aralkyl, alkylarylene, arylheterocyclyl, alkoxyarylene, aryloxyalkylene, cycloalkoxyalkylene, alkoxycarbonylalkylene, and alkylcarbonylheterocyclyl groups are optionally substituted with one or more radicals independently selected from alkyl, halo, haloalkyl, alkoxy, haloalkoxy, keto, amino, nitro, and cyano; or R35 is CHR48R49 wherein R48 is arylsulfonylamino or alkylarylsulfonylamino, and R49 is selected from aralkyl, amino, alkylamino, and aralkylamino; or R35 is —NR50R51 wherein R50 is alkyl, and R51 is aryl; and wherein R36 is selected from alkyl, haloalkyl, aryl, heterocyclyl, cycloalkylalkylene, alkylarylene, alkenylarylene, arylarylene, aralkyl, aralkenyl, heterocyclylheterocyclyl, carboxyarylene, alkoxyarylene, alkoxycarbonylarylene, alkylcarbonylaminoarylene, alkylcarbonylaminoheterocyclyl, arylcarbonylaminoalkylheterocyclyl, alkylaminoarylene, alkylamino, alkylaminoarylene, alkylsulfonylarylene, alkylsulfonylaralkyl, and arylsulfonylheterocyclyl; wherein said aryl, heterocyclyl, cycloalkylalkylene, aralkyl, alkylcarbonylaminoheterocyclyl, and alkylsulfonylarylene groups are optionally substituted with one or more radicals independently selected from alkyl, halo, hydroxy, haloalkyl, alkoxy, haloalkoxy, keto, amino, nitro, and cyano; and wherein R37 is selected from hydrogen and alkyl; and wherein R38 is selected from hydrogen, alkyl, alkenyl, aryl, heterocyclyl, aralkyl, alkylarylene, arylcycloalkyl, arylarylene, cycloalkylalkylene, heterocyclylalkylene, alkylheterocyclylalkylene, aralkylheterocyclyl, alkoxyalkylene, alkoxyarylene, aryloxyarylene, arylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkylene, alkoxycarbonylarylene, alkylcarbonylcarbonylalkylene, alkylaminoalkylene, alkylaminoaralkyl, alkylcarbonylaminoalkylene, alkylthioarylene, alkylsulfonylaralkyl, and aminosulfonylaralkyl; wherein said aryl, heterocyclyl, aralkyl, and heterocyclylalkylene groups are optionally substituted with one or more radicals independently selected from alkyl, halo, hydroxy, haloalkyl, alkoxy, haloalkoxy, keto, amino, nitro, and cyano; or R38 is —CR52R53 wherein R52 is alkoxycarbonyl, and R53 is alkylthioalkylene; or R37 and R38 together with the nitrogen atom to which they are attached form a heterocycle; and R39 and R40 have the same definition as R26 and R27 in claim 1; or R2 is —CR54R55 wherein R54 is phenyl and R55 is hydroxy; or R2 is selected from the group consisting of 5898wherein
k is an integer from 0 to 3; and R56 is hydrogen or lower alkyl; and R57 is hydrogen or lower alkyl; or R56 and R57 form a lower alkylene bridge; and R58 is selected from hydrogen, alkyl, aralkyl, aryl, heterocyclyl, heterocyclylalkyl, alkoxycarbonyl, alkylsulfonyl, aralkylsulfonyl, arylsulfonyl, —C(O)R59, —SO2R60, and —C(O)NHR61; wherein R59 is selected from alkyl, haloalkyl, cycloalkyl, aryl, heterocyclyl, alkylarylene, aralkyl, alkylheterocyclyl, alkoxy, alkenoxy, aralkoxy, alkoxyalkylene, alkoxyarylene, alkoxyaralkyl; wherein said aryl, heterocyclyl, and aralkyl groups are optionally substituted with one or more radicals independently selected from alkyl, halo, hydroxy, haloalkyl, alkoxy, haloalkoxy, keto, amino, nitro, and cyano; and wherein R60 is selected from alkyl, aryl, heterocyclyl, alkylarylene, alkylheterocyclyl, aralkyl, heterocyclylheterocyclyl, alkoxyarylene, alkylamino, alkylaminoarylene, alkylsulfonylarylene, and arylsulfonylheterocyclyl; wherein said aryl, heterocyclyl, and aralkyl groups are optionally substituted with one or more radicals independently selected from alkyl, halo, hydroxy, haloalkyl, alkoxy, haloalkoxy, keto, amino, nitro, and cyano; and wherein R61 is selected from alkyl, aryl, alkylarylene, and alkoxyarylene; wherein said aryl group is optionally substituted with one or more radicals independently selected from alkyl, halo, hydroxy, haloalkyl, alkoxy, haloalkoxy, keto, amino, nitro, and cyano; and R3 is selected from pyridinyl, pyrimidinyl, quinolinyl, purinyl, and 5899wherein R43 is selected from hydrogen, lower alkyl, lower aminoalkyl, lower alkoxyalkyl, lower alkenoxyalkyl and lower aryloxyalkyl; and wherein the R3 pyridinyl, pyrimidinyl, quinolinyl and purinyl groups are optionally substituted with one or more radicals independently selected from lower alkylthio, lower alkylsulfonyl, aminosulfonyl, halo, lower alkyl, lower aralkyl, lower phenylalkenyl, lower phenylheterocyclyl, carboxy, lower alkylsulfinyl, cyano, lower alkoxycarbonyl, aminocarbonyl, lower alkylcarbonylamino, lower haloalkyl, hydroxy, lower alkoxy, amino, lower cycloalkylamino, lower alkylamino, lower alkenylamino, lower alkynylamino, lower aminoalkyl, arylamino, lower aralkylamino, nitro, halosulfonyl, lower alkylcarbonyl, lower alkoxycarbonylamino, lower alkoxyphenylalkylamino, lower alkylaminoalkylamino, lower hydroxyalkylamino, lower heterocyclylamino, lower heterocyclylalkylamino, lower phenylalkylheterocyclylamino, lower alkylaminocarbonyl, lower alkoxyphenylalkylamino, hydrazinyl, lower alkylhydrazinyl, or —NR62R63 wherein R62 is lower alkylcarbonyl or amino, and R63 is lower alkyl or lower phenylalkyl; and R4 is selected from hydrido, lower cycloalkyl, lower cycloalkenyl, aryl selected from phenyl, biphenyl, and naphthyl, and 5- or 6-membered heterocyclyl; wherein the lower cycloalkyl, lower cycloalkenyl, aryl and 5-10 membered heterocyclyl groups of R4 are optionally substituted with one or more radicals independently selected from lower alkylthio, lower alkylsulfonyl, lower alkylsulfinyl, halo, lower alkyl, lower alkynyl, lower alkoxy, lower aryloxy, lower aralkoxy, lower heterocyclyl, lower haloalkyl, amino, cyano, nitro, lower alkylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 3. A compound of claim 2 wherein
R1 is selected from hydrido, methyl, ethyl, propyl, isopropyl, tert-butyl, isobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, ethenyl, propenyl, ethynyl, propargyl, 1-propynyl, 2-propynyl, piperidinyl, piperazinyl, morpholinyl, benzyl, phenylethyl, morpholinylmethyl, morpholinylethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridinylmethyl, thienylmethyl, methoxymethyl, ethoxymethyl, amino, methylamino, dimethylamino, phenylamino, methylaminomethyl, dimethylaminomethyl, methylaminoethyl, dimethylaminoethyl, ethylaminoethyl, diethylaminoethyl, cyclopropyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, hydroxymethyl, hydroxyethyl, mercaptomethyl, and methylthiomethyl; and R2 is selected from hydrido, chloro, fluoro, bromo, methyl, ethyl, propyl, isopropyl, tert-butyl, isobutyl, phenyl, biphenyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxymethyl, hydroxyethyl, pyridinyl, isothiazolyl, isoxazolyl, thienyl, thiazolyl, oxazolyl, pyrimidinyl, quinolyl, isoquinolinyl, imidazolyl, benzimidazolyl, furyl, pyrazinyl, piperidinyl, piperazinyl, morpholinyl, N-methylpiperazinyl, methoxycarbonylethyl, ethoxycarbonylethyl, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, N-n-propylamino, N,N-dimethylamino, N-methyl-N-phenylamino, N-phenylamino, piperadinylamino, N-benzylamino, N-propargylamino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, aminomethyl, aminoethyl, aminoethylamino, aminopropylamino, N,N-dimethylaminoethylamino, N,N-dimethylaminopropylamino, morpholinylethylamino, morpholinylpropylamino, carboxymethylamino, methoxyethylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, 1,1-dimethylethoxycarbonyl, 1,1-dimethylethoxycarbonylaminoethylamino, 1,1-dimethylethoxycarbonylaminopropylamino, piperazinylcarbonyl, and 1,1-dimethylethoxycarbonylpiperazinylcarbonyl; wherein the aryl, heteroaryl, cycloalkyl and cycloalkenyl groups are so optionally substituted with one or more radicals independently selected from fluoro, chloro, bromo, keto, methyl, ethyl, isopropyl, tert-butyl, isobutyl, benzyl, carboxy, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, fluoromethyl, difluoromethyl, dimethylamino, methoxycarbonyl, ethoxycarbonyl, and 1,1-dimethylethylcarbonyl; or R2 is —CR54R55 wherein R54 is phenyl and R55 is hydroxy; and R3 is selected from pyridinyl, pyrimidinyl, and purinyl; wherein R3 is optionally substituted with one or more radicals independently selected from methylthio, methylsulfinyl, methylsulfonyl, fluoro, chloro, bromo, aminosulfonyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, cyano, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, methylcarbonylamino, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, dichloromethyl, chloromethyl, hydroxy, fluorophenylmethyl, fluorophenylethyl, chlorophenylmethyl, chlorophenylethyl, fluorophenylethenyl, chlorophenylethenyl, fluorophenylpyrazolyl, chlorophenylpyrazolyl, carboxy, methoxy, ethoxy, propyloxy, n-butoxy, methylamino, ethylamino, dimethylamino, diethylamino, 2-methylbutylamino, propargylamino, aminomethyl, aminoethyl, N-methyl-N-phenylamino, phenylamino, diphenylamino, benzylamino, phenethylamino, cyclopropylamino, nitro, chlorosulfonyl, amino, methylcarbonyl, methoxycarbonylamino, ethoxycarbonylamino, methoxyphenylmethylamino, N,N-dimethylaminoethylamino, hydroxypropylamino, hydroxyethylamino, imidazolylethylamino, morpholinylethylamino, (1-ethyl-2-hydroxy)ethylamino, piperidinylamino, pyridinylmethylamino, phenylmethylpiperidinylamino, phenylmethylamino, fluorophenylmethylamino, fluorophenylethylamino, methylaminocarbonyl, ethylaminocarbonyl, methylcarbonyl, methoxyphenylmethylamino, hydrazinyl, 1-methylhydrazinyl, or —NR62R63 wherein R62 is methylcarbonyl or amino, and R63 is methyl, ethyl or phenylmethyl; and R4 is selected from hydrido, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, phenyl, biphenyl, morpholinyl, pyrrolidinyl, piperazinyl, piperidinyl, pyridinyl, thienyl, isothiazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, quinolyl, isoquinolinyl, imidazolyl, benzimidazolyl, furyl, pyrazinyl, dihydropyranyl, dihydropyridinyl, dihydrofuryl, tetrahydropyranyl, tetrahydrofuryl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein the cycloalkyl, cycloalkenyl, aryl and heterocyclyl groups of R4 are optionally substituted with one or more radicals independently selected from methylthio, methylsulfinyl, methylsulfonyl, fluoro, chloro, bromo, methyl, ethyl, isopropyl, tert-butyl, isobutyl, ethynyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, fluoromethyl, difluoromethyl, amino, cyano, nitro, dimethylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 4. A compound of claim 3 wherein
R1 is hydrido, methyl, ethyl, propargyl, hydroxyethyl, dimethylaminoethyl, diethylaminoethyl or morpholinylethyl; R2 is selected from hydrido, methyl, ethyl, propyl, phenyl, trifluoromethyl, methoxycarbonylethyl, N,N-dimethylamino, N-phenylamino, piperidinyl, piperazinyl, pyridinyl, N-methylpiperazinyl, and piperazinylamino; wherein the phenyl, piperidipyl, and pyridinyl groups are optionally substituted with one or more radicals independently selected from fluoro, chloro, bromo, methyl, ethyl, and trifluoromethyl; R3 is selected from pyridinyl, pyrimidinyl or quinolinyl; wherein R3 is optionally substituted with one or more radicals independently selected from fluoro, bromo, methyl, cyano, methoxycarbonyl, aminocarbonyl, benzyl, phenethyl, acetyl, hydroxyl, methoxy, dimethylamino, benzylamino, phenethylamino, aminomethyl, amino, hydroxy, and methylcarbonyl; R4 is selected from phenyl, quinolyl, biphenyl, pyridinyl, thienyl, furyl, dihydropyranyl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein the cycloalkyl, cycloalkenyl, aryl and heterocyclyl groups of R4 are optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 5. A compound of claim 4 wherein
R1 is hydrido or methyl; R2 is selected from hydrido, methyl or ethyl; R3 is selected from pyridinyl, pyrimidinyl or quinolinyl; wherein R3 is optionally substituted with one or more radicals independently selected from fluoro, bromo, methyl, cyano, methoxycarbonyl, aminocarbonyl, benzyl, phenethyl, acetyl, hydroxyl, methoxy, dimethylamino, benzylamino, phenethylamino, aminomethyl, amino, hydroxy, and methylcarbonyl; R4 is selected from phenyl which is optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 6. A compound of claim 2 wherein
R1 is selected from hydrido, methyl, ethyl, propyl, isopropyl, tert-butyl, isobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, ethenyl, propenyl, ethynyl, propargyl, 1-propynyl, 2-propynyl, piperidinyl, piperazinyl, morpholinyl, benzyl, phenylethyl, morpholinylmethyl, morpholinylethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridinylmethyl, thienylmethyl, methoxymethyl, ethoxymethyl, amino, methylamino, dimethylamino, phenylamino, methylaminomethyl, dimethylaminomethyl, methylaminoethyl, dimethylaminoethyl, ethylaminoethyl, diethylaminoethyl, cyclopropyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, hydroxymethyl, hydroxyethyl, mercaptomethyl, and methylthiomethyl; and R2 has the formula: 5900wherein:
j is 0, 1 or 2; and m is 0; and R30 and R31 are independently selected from hydrogen and lower alkyl; R32 is selected from hydrogen, lower alkyl, lower phenylalkyl, lower heterocyclylalkyl, lower alkoxyalkylene, aryloxyalkylene, aminoalkyl, lower alkylaminoalkyl, lower phenylaminoalkyl, lower alkylcarbonylalkylene, lower phenylcarbonylalkylene, and lower heterocyclylcarbonylaminoalkylene; R33 is selected from hydrogen, lower alkyl, —C(O)R35, —C(O)OR35, —SO2R36, —C(O)NR37R38, and —SO2NR39R40; wherein R35 is selected from lower alkyl, lower cycloalkyl, lower haloalkyl, lower alkenyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower phenylalkyl, lower phenylcycloalkyl, lower cycloalkenylalkylene, lower heterocyclylalkylene, lower alkylphenylene, lower alkylheterocyclyl, phenylphenylene, lower phenylheterocyclyl, lower alkoxy, lower alkenoxy, lower alkoxyalkylene, lower alkoxyphenylalkyl, lower alkoxyphenylene, lower phenoxyalkylene, lower phenylalkoxyalkylene, lower cycloalkyloxyalkylene, lower alkoxycarbonyl, lower heterocyclylcarbonyl, lower alkylcarbonyloxyalkylene, lower alkylcarbonyloxyphenylene, lower alkoxycarbonylalkylene, lower alkoxycarbonylphenylene, lower phenylalkoxycarbonylheterocyclyl, lower alkylcarbonylheterocyclyl, lower phenylcarbonyloxyalkylphenylene, and lower alkylthioalkylene; wherein said aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower phenylalkyl, lower alkylphenylene, lower phenylheterocyclyl, lower alkoxyphenylene, lower phenoxyalkylene, lower cycloalkoxyalkylene, lower alkoxycarbonylalkylene, and lower alkylcarbonylheterocyclyl groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; or R35 is CHR48R49 wherein R48 is phenylsulfonylamino or lower alkylphenylsulfonylamino, and R49 is selected from lower phenylalkyl, amino, lower alkylamino, and lower phenylalkylamino; or R35 is —NR50R51 wherein R50 is lower alkyl, and R51 is aryl selected from phenyl, biphenyl and naphthyl; and wherein R36 is selected from lower alkyl, lower haloalkyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower cycloalkylalkylene, lower alkylphenylene, lower alkenylphenylene, phenylphenylene, lower phenylalkyl, lower phenylalkenyl, lower heterocyclylheterocyclyl, carboxyphenylene, lower alkoxyphenylene, lower alkoxycarbonylphenylene, lower alkylcarbonylaminophenylene, lower alkylcarbonylaminoheterocyclyl, lower phenylcarbonylaminoalkylheterocyclyl, lower alkylaminophenylene, lower alkylamino, lower alkylaminophenylene, lower alkylsulfonylphenylene, lower alkylsulfonylphenylalkyl, and lower phenylsulfonylheterocyclyl; wherein said aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower cycloalkylalkylene, lower phenylalkyl, lower alkylcarbonylaminoheterocyclyl, and lower alkylsulfonylphenylene groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; and wherein R37 is selected from hydrogen and lower alkyl; and wherein R38 is selected from hydrogen, lower alkyl, lower alkenyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower phenylalkyl, lower alkylphenylene, lower phenylcycloalkyl, phenylphenylene, lower cycloalkylalkylene, lower heterocyclylalkylene, lower alkylheterocyclylalkylene, lower phenylalkylheterocyclyl, lower alkoxyalkylene, lower alkoxyphenylene, lower phenoxyphenylene, phenylcarbonyl, lower alkoxycarbonyl, lower alkoxycarbonylalkylene, lower alkoxycarbonylphenylene, lower alkylcarbonylcarbonylalkylene, lower alkylaminoalkylene, lower alkylaminophenylalkyl, lower alkylcarbonylaminoalkylene, lower alkylthiophenylene, lower alkylsulfonylphenylalkyl, and lower aminosulfonylphenylalkyl; wherein said aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower phenylalkyl, and lower heterocyclylalkylene groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; or R38 is —CR52R53 wherein R52 is lower alkoxycarbonyl, and R53 is lower alkylthioalkylene; or R37 and R38 together with the nitrogen atom to which they are attached form a 4-8 membered ring heterocycle; R39 and R40 have the same definition as R26 and R27 in claim 2; or R2 is selected from the group consisting of 5901wherein
k is an integer from 0 to 2; and R56 is hydrogen or lower alkyl; and R57 is hydrogen or lower alkyl; and R58 is selected from hydrogen, lower alkyl, lower phenylalkyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower heterocyclylalkyl, lower alkoxycarbonyl, lower alkylsulfonyl, lower phenylalkylsulfonyl, lower phenylsulfonyl, —C(O)R59, —SO2R60, and —C(O)NHR61; wherein R59 is selected from lower alkyl, lower haloalkyl, lower cycloalkyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower alkylphenylene, lower phenylalkyl, lower alkylheterocyclyl, lower alkoxy, lower alkenoxy, loewr phenylalkoxy, lower alkoxyalkylene, lower alkoxyphenylene, lower alkoxyphenylalkyl; wherein said aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, and lower phenylalkyl groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; and wherein R60 is selected from lower alkyl, aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, lower alkylphenylene, lower alkylheterocyclyl, lower phenylalkyl, lower heterocyclylheterocyclyl, lower alkoxyphenylene, lower alkylamino, lower alkylaminophenylene, lower alkylsulfonylphenylene, and lower phenylsulfonylheterocyclyl; wherein said aryl selected from phenyl, biphenyl and naphthyl, lower heterocyclyl, and lower phenylalkyl groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; and wherein R61 is selected from lower alkyl, aryl selected from phenyl, biphenyl and napthyl, lower alkylphenylene, and lower alkoxyphenylene; wherein said aryl group is optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; and R3 is selected from pyridinyl, pyrimidinyl, and purinyl; wherein R3 is optionally substituted with one or more radicals independently selected from methylthio, methylsulfinyl, methylsulfonyl, fluoro, chloro, bromo, aminosulfonyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, cyano, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, methylcarbonylamino, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, dichloromethyl, chloromethyl, hydroxy, fluorophenylmethyl, fluorophenylethyl, chlorophenylmethyl, chlorophenylethyl, fluorophenylethenyl, chlorophenylethenyl, fluorophenylpyrazolyl, chlorophenylpyrazolyl, carboxy, methoxy, ethoxy, propyloxy, n-butoxy, methylamino, ethylamino, dimethylamino, diethylamino, 2-methylbutylamino, propargylamino, aminomethyl, aminoethyl, N-methyl-N-phenylamino, phenylamino, diphenylamino, benzylamino, phenethylamino, cyclopropylamino, nitro, chlorosulfonyl, amino, methylcarbonyl, methoxycarbonylamino, ethoxycarbonylamino, methoxyphenylmethylamino, N,N-dimethylaminoethylamino, hydroxypropylamino, hydroxyethylamino, imidazolylethylamino, morpholinylethylamino, (1-ethyl-2-hydroxy)ethylamino, piperidinylamino, pyridinylmethylamino, phenylmethylpiperidinylamino, phenylmethylamino, fluorophenylmethylamino, fluorophenylethylamino, methylaminocarbonyl, ethylaminocarbonyl, methylcarbonyl, methoxyphenylmethylamino, hydrazinyl, 1-methylhydrazinyl, or —NR62R63 wherein R62 is methylcarbonyl or amino, and R63 is methyl, ethyl or phenylmethyl; and R4 is selected from hydrido, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, phenyl, biphenyl, morpholinyl, pyrrolidinyl, piperazinyl, piperidinyl, pyridinyl, thienyl, isothiazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, quinolyl, isoquinolinyl, imidazolyl, benzimidazolyl, furyl, pyrazinyl, dihydropyranyl, dihydropyridinyl, dihydrofuryl, tetrahydropyranyl, tetrahydrofuryl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein the cycloalkyl, cycloalkenyl, aryl and heterocyclyl groups of R4 are optionally substituted with one or more radicals independently selected from methylthio, methylsulfinyl, methylsulfonyl, fluoro, chloro, bromo, methyl, ethyl, isopropyl, tert-butyl, isobutyl, ethynyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, fluoromethyl, difluoromethyl, amino, cyano, nitro, dimethylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 7. A compound of claim 6 wherein
R1 is hydrido, methyl, ethyl, propargyl, hydroxyethyl, dimethylaminoethyl, diethylaminoethyl or morpholinylethyl; R2 has the formula: 5902wherein:
j is 0, 1 or 2; and m is 0; and R30 is hydrogen; and R31 is selected from hydrogen and lower alkyl; and R32 is selected from hydrogen and lower alkyl; and R33 is selected from lower alkyl, —C(O)R35, —C(O)OR35, —SO2R36, —C(O)NR37R38, and —SO2NR39R40; wherein R35 is selected from lower alkyl, lower cycloalkyl, phenyl, lower heterocyclyl, lower alkylphenylene, lower alkoxy, lower alkenoxy, lower alkoxyalkylene, lower phenoxyalkylene, and lower phenylalkoxyalkylene; wherein said phenyl and lower phenoxyalkylene groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, and lower haloalkyl; and wherein R36 is selected from lower alkyl, phenyl, lower heterocyclyl, lower alkylphenylene, phenylphenylene, lower phenylalkyl, lower alkylheterocyclyl, lower heterocyclylheterocyclyl, lower alkoxyphenylene, and lower alkylamino; wherein said phenyl and lower heterocyclyl groups are optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; and wherein R37 is hydrogen; and wherein R38 is selected from lower alkyl, phenyl, and lower alkylphenylene; wherein R39 and R40 have the same definition as R26 and R27 in claim 2; or R2 is selected from the group consisting of 5903wherein
k is an integer from 0 or 1; and R56 is hydrogen; and R57 is hydrogen; and
R58 is selected from —C(O)R59 and —SO2R60; wherein R59 is selected from lower alkyl, lower cycloalkyl, phenyl, lower alkylphenylene, and lower alkoxyalkylene; wherein said phenyl group is optionally substituted with one or more radicals independently selected from lower alkyl, halo, hydroxy, lower haloalkyl, lower alkoxy, lower haloalkoxy, keto, amino, nitro, and cyano; and wherein R60 is selected from lower alkyl; and R3 is selected from pyridinyl, pyrimidinyl or quinolinyl; wherein R3 is optionally substituted with one or more radicals independently selected from fluoro, bromo, methyl, cyano, methoxycarbonyl, aminocarbonyl, benzyl, phenethyl, acetyl, hydroxyl, methoxy, dimethylamino, benzylamino, phenethylamino, aminomethyl, amino, hydroxy, and methylcarbonyl; and R4 is selected from phenyl, quinolyl, biphenyl, pyridinyl, thienyl, furyl, dihydropyranyl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein the cycloalkyl, cycloalkenyl, aryl and heterocyclyl groups of R4 are optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 8. A compound of claim 7 wherein
R1 is hydrido or methyl; and R3 is selected from pyridinyl, pyrimidinyl or quinolinyl; wherein R3 is optionally substituted with one or more radicals independently selected from fluoro, bromo, methyl, cyano, methoxycarbonyl, aminocarbonyl, benzyl, phenethyl, acetyl, hydroxyl, methoxy, dimethylamino, benzylamino, phenethylamino, aminomethyl, amino, hydroxy, and methylcarbonyl; and R4 is selected from phenyl which is optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; or a pharmaceutically-acceptable salt or tautomer thereof.
- 9. A compound of claim 1 wherein R1 is hydrido.
- 10. A compound of claim 2 wherein R1 is hydrido.
- 11. A compound of claim 3 wherein R1 is hydrido.
- 12. A compound of claim 6 wherein R1 is hydrido.
- 13. A compound of claim 3 wherein R1 is methyl or ethyl.
- 14. A compound of claim 6 wherein R1 is methyl or ethyl.
- 15. A compound of claim 2 wherein R2 is hydrido.
- 16. A compound of claim 3 wherein R2 is hydrido.
- 17. A compound of claim 2 wherein R4 is optionally substituted phenyl.
- 18. A compound of claim 3 wherein R4 is optionally substituted phenyl.
- 19. A compound of claim 6 wherein R4 is optionally substituted phenyl.
- 20. A compound of claim 2 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl.
- 21. A compound of claim 3 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl
- 22. A compound of claim 2 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl; and R4 is optionally substituted phenyl.
- 23. A compound of claim 3 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl; and R4 is optionally substituted phenyl.
- 24. A compound of Formula IX
- 25. A compound of claim 24 wherein
R1 is selected from hydrido, methyl, ethyl, hydroxyethyl and propargyl; and R2 is selected from hydrido, methyl, ethyl, propyl, phenyl, trifluoromethyl, hydroxyethyl, methoxycarbonylethyl, ethoxycarbonylethyl, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, N-propylamino, N-phenylamino, aminomethyl, aminoethyl, aminoethylamino, aminopropylamino, propargylamino, benzylamino, dimethylaminopropylamino, morpholinylpropylamino, morpholinylethylamino, piperidinyl, piperazinyl, imidazolyl, morpholinyl, pyridinyl, carboxymethylamino, methoxyethylamino, (1,1-dimethyl)ethylcarbonyl, (1,1-dimethyl)ethylcarbonylaminopropylamino, (1,1-dimethyl)ethylcarbonylaminoethylamino, piperazinylcarbonyl, 1,1-dimethylethylpiperazinylcarbonyl; wherein the phenyl, piperidinyl, piperazinyl, imidazolyl, morpholinyl, and pyridinyl groups are optionally substituted with one or more radicals independently selected from fluoro, chloro, bromo, keto, methyl, ethyl, trifluoromethyl, benzyl, methoxy, methoxycarbonyl, ethoxycarbonyl and (1,1-dimethyl)ethoxycarbonyl; and R4 is selected from cyclohexyl, cyclohexenyl, cyclohexadienyl, phenyl, quinolyl, biphenyl, pyridinyl, thienyl, furyl, dihydropyranyl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein R4 is optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; and R5 is selected from fluoro, chloro, bromo, methyl, fluorophenylethyl, fluorophenylethenyl, fluorophenylpyrazolyl, cyano, methoxycarbonyl, aminocarbonyl, acetyl, hydroxy, carboxy, methoxy, methylamino, dimethylamino, 2-methylbutylamino, ethylamino, dimethylaminoethylamino, hydroxypropylamino, hydroxyethylamino, imidazolylamino, morpholinylethylamino, (1-ethyl-2-hydroxy)ethylamino, piperidinylamino, pyridinylmethylamino, phenylmethylpiperidinylamino, aminomethyl, cyclopropylamino, amino, hydroxy, methylcarbonyl, ethoxycarbonylamino, methoxyphenylmethylamino, phenylmethylamino, fluorophenylmethylamino, fluorophenylethylamino, methylaminocarbonyl, methylcarbonyl, hydrazinyl, and 1-methylhydrazinyl, or —NR62R63 wherein R62 is methylcarbonyl or amino, and R63 is methyl or benzyl; or a pharmaceutically-acceptable salt or tautomer thereof.
- 26. A compound of claim 24 wherein R1 is hydrido.
- 27. A compound of claim 25 wherein R1 is hydrido.
- 28. A compound of claim 24 wherein R1 is lower alkyl.
- 29. A compound of claim 25 wherein R1 is lower alkyl.
- 30. A compound of claim 24 wherein R2 is hydrido.
- 31. A compound of claim 25 wherein R2 is hydrido.
- 32. A compound of claim 24 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl.
- 33. A compound of claim 25 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl.
- 34. A compound of claim 25 wherein Z represents a carbon atom.
- 35. A compound of Formula X
- 36. A compound of claim 35 wherein
R1 is selected from methyl, ethyl, hydroxyethyl and propargyl; and R2 is selected from methyl, ethyl, propyl, phenyl, trifluoromethyl, hydroxyethyl, methoxycarbonylethyl, ethoxycarbonylethyl, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, N-propylamino, N-phenylamino, aminomethyl, aminoethyl, aminoethylamino, aminopropylamino, propargylamino, benzylamino, piperadinylamino, dimethylaminoethylamino, dimethylaminopropylamino, morpholinylpropylamino, morpholinylethylamino, piperidinyl, piperazinyl, imidazolyl, morpholinyl, pyridinyl, N-methylpiperazinyl, carboxymethylamino, methoxyethylamino, (1,1-dimethyl)ethylcarbonyl, (1,1-dimethyl)ethylcarbonylaminopropylamino, (1,1-dimethyl)ethylcarbonylaminoethylamino, piperazinylcarbonyl, and 1,1-dimethylethylpiperazinylcarbonyl; wherein the phenyl, piperidinyl, piperazinyl, imidazolyl, morpholinyl, and pyridinyl groups are optionally substituted with one or more radicals independently selected from fluoro, chloro, bromo, keto, methyl, ethyl, trifluoromethyl, benzyl, methoxy, methoxycarbonyl, ethoxycarbonyl and (1,1-dimethyl)ethoxycarbonyl; and R4 is selected from phenyl, quinolyl, biphenyl, pyridinyl, thienyl, furyl, dihydropyranyl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein R4 is optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; and R5 is selected from fluoro, chloro, bromo, methyl, fluorophenylethyl, fluorophenylethenyl, fluorophenylpyrazolyl, cyano, methoxycarbonyl, aminocarbonyl, acetyl, hydroxy, carboxy, methoxy, methylamino, dimethylamino, 2-methylbutylamino, ethylamino, dimethylaminoethylamino, hydroxypropylamino, hydroxyethylamino, propargylamino, imidazolylamino, morpholinylethylamino, (1-ethyl-2-hydroxy)ethylamino, piperidinylamino, pyridinylmethylamino, phenylmethylpiperidinylamino, aminomethyl, cyclopropylamino, amino, hydroxy, methylcarbonyl, ethoxycarbonylamino, methoxyphenylmethylamino, phenylmethylamino, fluorophenylmethylamino, fluorophenylethylamino, methylaminocarbonyl, methylcarbonyl, hydrazinyl, and 1-methylhydrazinyl, or —NR62R63 wherein R62 is methylcarbonyl or amino, and R63 is methyl or benzyl; or a pharmaceutically-acceptable salt or tautomer thereof.
- 37. A compound of claim 35 wherein R1 is lower alkyl.
- 38. A compound of claim 36 wherein R1 is lower alkyl.
- 39. A compound of claim 35 wherein R2 is hydrido.
- 40. A compound of claim 36 wherein R2 is hydrido.
- 41. A compound of claim 35 wherein R1 is methyl or ethyl, and R2 is selected from hydrido, methyl and ethyl.
- 42. A compound of claim 36 wherein R1 is methyl or ethyl, and R2 is selected from hydrido, methyl and ethyl.
- 43. A compound of claim 35 wherein Z represents a carbon atom.
- 44. A compound of Formula XI
- 45. A compound of claim 44 wherein
R1 is selected from methyl, ethyl, hydroxyethyl and propargyl; and R2 is selected from methyl, ethyl, propyl, phenyl, trifluoromethyl, hydroxyethyl, methoxycarbonylethyl, ethoxycarbonylethyl, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, N-propylamino, N-phenylamino, aminomethyl, aminoethyl, aminoethylamino, aminopropylamino, propargylamino, benzylamino, dimethylaminopropylamino, morpholinylpropylamino, morpholinylethylamino, piperidinyl, piperazinyl, imidazolyl, morpholinyl, pyridinyl, carboxymethylamino, methoxyethylamino, (1,1-dimethyl)ethylcarbonyl, (1,1-dimethyl)ethylcarbonylaminopropylamino, (1,1-dimethyl)ethylcarbonylaminoethylamino, piperazinylcarbonyl, 1,1-dimethylethylpiperazinylcarbonyl; wherein the phenyl, piperidinyl, piperazinyl, imidazolyl, morpholinyl, and pyridinyl groups are optionally substituted with one or more radicals independently selected from fluoro, chloro, bromo, keto, methyl, ethyl, trifluoromethyl, benzyl, methoxy, methoxycarbonyl, ethoxycarbonyl and (1,1-dimethyl)ethoxycarbonyl; R4 is selected from phenyl, quinolyl, biphenyl, pyridinyl, thienyl, furyl, dihydropyranyl, benzofuryl, dihydrobenzofuryl, and benzodioxolyl; wherein R4 is optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; and R5 is selected from fluoro, chloro, bromo, methyl, fluorophenylethyl, fluorophenylethenyl, fluorophenylpyrazolyl, cyano, methoxycarbonyl, aminocarbonyl, acetyl, hydroxy, carboxy, methoxy, methylamino, dimethylamino, 2-methylbutylamino, ethylamino, dimethylaminoethylamino, hydroxypropylamino, hydroxyethylamino, imidazolylamino, morpholinylethylamino, (1-ethyl-2-hydroxy)ethylamino, piperidinylamino, pyridinylmethylamino, phenylmethylpiperidinylamino, aminomethyl, cyclopropylamino, amino, hydroxy, methylcarbonyl, ethoxycarbonylamino, methoxyphenylmethylamino, phenylmethylamino, fluorophenylmethylamino, fluorophenylethylamino, methylaminocarbonyl, methylcarbonyl, hydrazinyl, and 1-methylhydrazinyl, or —N62R63 wherein R62 is methylcarbonyl or amino, and R63 is methyl or benzyl; or a pharmaceutically-acceptable salt or tautomer thereof.
- 46. A compound of claim 44 wherein R1 is lower alkyl.
- 47. A compound of claim 45 wherein R1 is lower alkyl.
- 48. A compound of claim 44 wherein R2 is hydrido.
- 49. A compound of claim 45 wherein R2 is hydrido.
- 50. A compound of claim 44 wherein R1 is methyl or ethyl, and R2 is selected from hydrido, methyl and ethyl.
- 51. A compound of claim 45 wherein R1 is methyl or ethyl, and R2 is selected from hydrido, methyl and ethyl.
- 52. A compound of claim 44 wherein Z represents a carbon atom.
- 53. A compound of Formula IX
- 54. A compound of claim 53 wherein
R1 is selected from hydrido, methyl, ethyl, hydroxyethyl and propargyl; R2 is selected from methyl, ethyl, propyl, phenyl, trifluoromethyl, hydroxyethyl, methoxycarbonylethyl, ethoxycarbonylethyl, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, N-propylamino, N-phenylamino, aminomethyl, aminoethyl, aminoethylamino, aminopropylamino, propargylamino, benzylamino, dimethylaminopropylamino, morpholinylpropylamino, morpholinylethylamino, piperidinyl, piperazinyl, imidazolyl, morpholinyl, pyridinyl, carboxymethylamino, methoxyethylamino, (1,1-dimethyl)ethylcarbonyl, (1,1-dimethyl)ethylcarbonylaminopropylamino, (1,1-dimethyl)ethylcarbonylaminoethylamino, piperazinylcarbonyl, 1,1-dimethylethylpiperazinylcarbonyl; wherein the phenyl, piperidinyl, piperazinyl, imidazolyl, morpholinyl, and pyridinyl groups are optionally substituted with one or more radicals independently selected from fluoro, chloro, bromo, keto, methyl, ethyl, trifluoromethyl, benzyl, methoxy, methoxycarbonyl, ethoxycarbonyl and (1,1-dimethyl)ethoxycarbonyl; R4 is phenyl that is optionally substituted with one or more radicals independently selected from methylthio, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, phenoxy, benzyloxy, trifluoromethyl, nitro, dimethylamino, and hydroxy; and R5 is selected from fluoro, chloro, bromo, methyl, fluorophenylethyl, fluorophenylethenyl, fluorophenylpyrazolyl, cyano, methoxycarbonyl, aminocarbonyl, acetyl, hydroxy, carboxy, methoxy, methylamino, dimethylamino, 2-methylbutylamino, ethylamino, dimethylaminoethylamino, hydroxypropylamino, hydroxyethylamino, imidazolylamino, morpholinylethylamino, (1-ethyl-2-hydroxy)ethylamino, piperidinylamino, pyridinylmethylamino, phenylmethylpiperidinylamino, aminomethyl, cyclopropylamino, amino, hydroxy, methylcarbonyl, ethoxycarbonylamino, methoxyphenylmethylamino, phenylmethylamino, fluorophenylmethylamino, fluorophenylethylamino, methylaminocarbonyl, methylcarbonyl, hydrazinyl, and 1-methylhydrazinyl, or —NR62R63 wherein R62 is methylcarbonyl or amino, and R63 is methyl or benzyl; or a pharmaceutically-acceptable salt or tautomer thereof.
- 55. A compound of claim 53 wherein R1 is hydrido or lower alkyl.
- 56. A compound of claim 54 wherein R1 is hydrido or lower alkyl.
- 57. A compound of claim 53 wherein R1 is hydrido.
- 58. A compound of claim 54 wherein R1 is hydrido.
- 59. A compound of claim 53 wherein R2 is hydrido.
- 60. A compound of claim 54 wherein R2 is hydrido.
- 61. A compound of claim 53 wherein R4 is phenyl substituted with one or more fluoro, chloro or bromo.
- 62. A compound of claim 54 wherein R4 is phenyl substituted with one or more fluoro, chloro or bromo.
- 63. A compound of claim 53 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl.
- 64. A compound of claim 54 wherein R1 and R2 are selected independently from hydrido, methyl and ethyl.
- 65. A compound of claim 53 wherein Z represents a carbon atom.
- 66. A compound of Formula IX
- 67. A compound of claim 66 wherein
Z represents a carbon atom; and R1 is selected from hydrido, methyl, hydroxyethyl, propargyl; and R2 is hydrido; and R4 is selected from phenyl and benzodioxolyl; wherein phenyl is optionally substituted with one or more radicals independently selected from chloro, fluoro and bromo; and R5 is selected from hydrido, fluoro, and 1-methylhydrazinyl; or a pharmaceutically-acceptable salt or tautomer thereof.
- 68. A compound of claim 67 wherein
Z represents a carbon atom; and R1 is selected from hydrido and methyl; and R2 is hydrido; and R4 is selected from phenyl that is optionally substituted with one or more radicals independently selected from chloro, fluoro and bromo; and R5is selected from hydrido and fluoro; or a pharmaceutically-acceptable salt or tautomer thereof.
- 69. A compound of claim 1 selected from compounds, their tautomers and their pharmaceutically acceptable salts, of the group consisting of
4-[5-(3-fluoro-4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine; 4-[5-methyl-3-(2-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-fluorophenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-methyl-3-(4-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[5-methyl-3-[4-(methylthio)phenyl]-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorohpenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(2,5-dimethylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(1,3-benzodioxol-5-yl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-(4-phenoxyphenyl)-1H-pyrazol-4-yl]pyridine; 4-[5-[(1,1′-biphenyl)-4-yl]-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-[3-(phenoxyphenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-[3-(phenylmethoxy)phenyl]-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-[2-(phenylmethoxy)phenyl]-1H-pyrazol-4-yl]pyridine; 2-[3-methyl-4-(4-pyridinyl)-1H-pyrazol-4-yl]phenol; 3-[3-methyl-4-(4-pyridinyl)-1H-pyrazol-4-yl]phenol; 1-hydroxy-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl]pyridinium; 5-(4-fluorophenyl)-N,N-dimethyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 5-(4-fluorophenyl)-N-phenyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 4-[5-(4-fluorophenyl)-3-phenyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyridine;4-[3-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]pyridine; 4-(5-cyclohexyl)-3-methyl-1H-pyrazol-4-yl)pyridine; 4-[5-(3-fluoro-5-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-methylphenyl)-3-propyl-1H-pyrazol-4-yl]pyridine; 4-[(3-methyl-5-phenyl-1H-pyrazol-4-yl)methyl]pyridine; 4-[3,5-bis(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[4-methyl-2-(2-trifluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(2-chlorophenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-methyl-3-(2,4-dimethylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(4-chlorophenyl)-1,3-dimethyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3-fluoro-2-methylphenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3,5-dimethylphenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3,5-dimethoxyphenyl)-5-methyl-1H-pyrazol-4-yl)pyridine; 4-[5-methyl-3-(3-nitrophenyl)-1H-pyrazol-4-yl]pyridine; N,N-dimethyl-4-[5-methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl]benzenamine; 4-[3-(2,3-dihydrobenzofuran-5-yl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-bromophenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(2-fluorophenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3-fluorophenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]pyridine; 4-(3-ethyl-4-phenyl-1H-pyrazol-4-yl)pyridine; 4-[5-(3-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl)pyridine; 4-[3-ethyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(3,4-difluorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-ethoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]pyridine; 4-[3-methyl-5-(3-thienyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-chloro-4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; ethyl 3-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazole-5-propanoate; 4-[3-(4-fluorophenyl)-1-methyl-pyrazol-4-yl]pyridine; 5-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyrimidin-2-amine; 5-[3-methyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyrimidin-2-amine; 5-[3-methyl-5-(2-methylphenyl)-1H-pyrazol-4-yl]pyrimidin-2-amine; 5-[5-(4-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyrimidin-2-amine; 5-[5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]pyrimidin-2-amine; 5-[5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyrimidin-2-amine;
5-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 4-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 4-[5-(3-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 4-[5-(2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 4-[5-(4-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 4-[5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 4-[5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-amine; 5-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]-2-methoxypyridine; 2-methoxy-5-[3-methyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 2-methoxy-5-[5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]-2-methoxypyridine; 2-methoxy-4-[3-methyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 2-methoxy-4-[3-methyl-5-(2-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(4-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]-2-methoxypyridine; 4-[5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2-methoxypyridine; 2-methoxy-4-[3-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]pyridine; 5-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 4-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 4-[5-(3-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 4-[5-(2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 4-[5-(4-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 4-[5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 4-[5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridin-2-ol; 5-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 4-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 4-[5-(3-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 4-[5-(2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 4-[5-(4-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 4-[5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 4-[5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-methanamine; 5-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(3-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(3-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(2-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(4-chlorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine-2-carboxamide; 4-[5-(3-fluoro-4-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(4-fluoro-3-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(4-chloro-3-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(2,3-dihydrobenzofuran-6-yl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(benzofuran-6-yl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-fluoro-5-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-chloro-5-methoxyphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(1-cyclohexyen-1-yl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(1,3-cyclohexadien-1-yl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(5,6-dihydro-2H-pyran-4-yl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-(5-cyclohexyl-3-methyl-1H-pyrazol-4-yl)pyridine; 4-[5-(4-methoxy-3-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-methoxy-4-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-methoxy-5-methylphenyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-furyl)-3-methyl-1H-pyrazol-4-yl]pyridine; 2-methyl-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine; 2-methoxy-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine; methyl 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyri-dine-2-carboxylate; 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine-2-carboxamide; 1-[4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridin-2-yl]ethanone; N,N-dimethyl-4-(3-methyl-5-phenyl-1H-pyrazol-2-yl)pyridin-2-amine; 3-methyl-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine; 3-methoxy-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine; methyl 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine-3-carboxylate; 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine-3-carboxamide; 1-[4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridin-3-yl]ethanone; 3-bromo-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyridine; N,N-dimethyl-4-(3-methyl-5-phenyl-1H-pyrazol-2-yl)pyridin-3-amine; 2-methyl-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyrimidine; 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyrimidine; 2-methoxy-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyrimidine; 4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyrimidin-2-amine; N,N-dimethyl-4-(3-methyl-5-phenyl-1H-pyrazol-4-yl)pyrimidin-2-amine; 4-(5,6-dihydro-2H-pyran-4-yl)-3-methyl-5-phenyl-1H-pyrazole; 3-methyl-5-phenyl-4-(3-thienyl)-1H-pyrazole; 4-(3-furyl)-3-methyl-5-phenyl-1H-pyrazole; 3-methyl-5-phenyl-4-(2-thienyl)-1H-pyrazole; 4-(2-furyl)-3-methyl-5-phenyl-1H-pyrazole; 4-(3-isothiazolyl)-3-methyl-5-phenyl-1H-pyrazole 4-(3-isoxazolyl)-3-methyl-5-phenyl-1H-pyrazole; 4-(5-isothiazolyl)-3-methyl-5-phenyl-1H-pyrazole; 4-(5-isoxazolyl)-3-methyl-5-phenyl-1H-pyrazole; 3-methyl-5-phenyl-4-(5-thiazolyl)-1H-pyrazole; 3-methyl-4-(5-oxazolyl)-5-phenyl-1H-pyrazole; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine; 2-methyl-4-[3-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-(1-methyl-3-phenyl-1H-pyrazol-4-yl)pyridine; 4-(3-phenyl-1H-pyrazol-4-yl)pyridine; 2-methyl-4-(3-phenyl-1H-pyrazol-4-yl)pyridine; 4-[3-(3-chlorophenyl)-1-methyl-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1-methyl-pyrazol-4-yl]pyridine; 4-[3-(3-chlorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(3-chlorophenyl)-1H-pyrazol-4-yl]-2-methylpyridine; 4-[3-(3-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3-fluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(3-chlorophenyl)-1-methyl-pyrazol-4-yl]-2-methylpyridine; 5-(4-chlorophenyl)-N-phenyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 5-(4-chlorophenyl)-N-methyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 5-(4-chlorophenyl)-N,N-dimethyl-4-(4-pyridinyl)-1H-pyrazol-3-amine dihydrate; 5-(3-fluorophenyl)-N,N-dimethyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; N,N-dimethyl-5-(3-methylphenyl)-4-(4-pyridinyl)-1H-pyrazol-3-amine; N-methyl-5-(3-methylphenyl)-4-(4-pyridinyl)-1H-pyrazol-3-amine; N-ethyl-5-(3-methylphenyl)-4-(4-pyridinyl)-1H-pyrazol-3-amine; N,N-diethyl-5-(3-methylphenyl)-4-(4-pyridinyl)-1H-pyrazol-3-amine; 5-(4-chlorophenyl)-N,N-diethyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 4-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]morpholine; 5-(4-chlorophenyl)-N-propyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 5-(4-chlorophenyl)-N-(phenylmethyl)-4-(4-pyridinyl)-1H-pyrazol-3-amine hydrate (2:1); 5-(4-chlorophenyl)-N-(2-methoxyethyl)-4-(4-pyridinyl)-1H-pyrazol-3-amine monohydrate; 1,1-dimethylethyl-4-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1-piperazinecarboxylate; 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]piperazine trihydrochloride; 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl)-4-methylpiperazine; 1,1-dimethylethyl 4-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1-piperazinecarboxylate; 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]piperazine trihydrochloride; 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]piperazine; N-[5-(4-chlorophenyl)-4-[2-(phenylmethyl)amino]-4-pyridinyl]-1H-pyrazol-3-yl]-1,3-propanediamine, trihydrochloride; 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-(phenylmethyl)piperazine; 4-[3-(4-fluorophenyl)-5-(1-piperazinyl)-1H-pyrazol-4-yl]pyrimidine, dihydrochloride; 1,1-dimethylethyl[3-[[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]amino]propyl]carbamate; N-[5-[4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1,3-propanediamine, trihydrochloride monohydrate; 1,1-dimethylethyl[2-[[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]amino]ethyl]carbamate; 1,1-dimethylethyl 4-[5-(4-chlorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1-piperazinecarboxylate; 1,1-dimethylethyl 4-[5-(4-fluorophenyl)-4-(4-pyrimidinyl)-1H-pyrazol-3-yl]-1-piperazinecarboxylate; 1,1-dimethylethyl[3-[[5-(4-chlorophenyl)-4-(2-fluoro-4-pyridinyl)-1H-pyrazol-3-yl]amino]propyl]carbamate; 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-ethylpiperazine; N-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1,2-ethanediamine; 4-[3-(2,6-difluorophenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3-ethylphenyl)-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3-chlorophenyl)-5-ethyl-1H-pyrazol-4-yl]pyridine; 4-[3-ethyl-5-(3-ethylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-5-(1-methylethyl)-1H-pyrazol-4-yl]pyridine; 4-[3-cyclopropyl-5-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(cyclopropyl-3-(4-(fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 5-cyclopropyl-3-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-1-ethanol; 3-(4-fluorophenyl)-5-(2-methoxy-4-pyridinyl)-4-(4-pyridinyl)-1H-pyrazole-1-ethanol; 4-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]-2(1H)-pyridinone; 1-acetyl-4-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]-2(1H)-pyridinone; Ethyl 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylate; 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid; 3-(4-fluorophenyl)-5-(4-imidazolyl)-4-(4-pyridinyl)-1H-pyrazole-1-ethanol; 4-[3-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl]pyridine 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-carboxylic acid; 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-methanol; 1-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]piperazine; 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]-1-piperazinecarboxylate; 4-(1,5-dimethyl-3-phenyl-1H-pyrazol-4-yl)pyridine; 4-(1,3-dimethyl-5-phenyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1,5-dimethyl-1H-pyrazol-4-yl]pyridine; 4-[5-(4-chlorophenyl)-1,3-dimethyl-1H-pyrazol-4-yl]pyridine; 4-[5-ethyl-1-methyl-3-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-ethyl-1-methyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1-ethyl-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-2-ethyl-5-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(2-chlorophenyl)-1H-pyrazol-4-yl]pyridine; 3-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-1-ethanol; 3-(4-fluorophenyl)-4-(4-pyrimidinyl)-1H-pyrazole-1-ethanol; 4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 2-[[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]amino]-1-butanol; 4-[5-bromo-3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinecarbonitrile; 4-[2-[3-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-1-yl]ethyl]morpholine; 3-(4-fluorophenyl)-1-methyl-α-phenyl-4-(4-pyridinyl)-1H-pyrazole-5-methanol; N-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-morpholineethanamine; 4-[3-(3-chlorophenyl)-1H-pyrazol-4-yl]-2(1H)-pyridinone hydrazone; 4-[3-(3-chlorophenyl)-1H-pyrazol-4-yl]-N-(phenylmethyl)-2-pyridinamine; 4-[3-(3-chlorophenyl)-1H-pyrazol-4-yl]-N-(phenylethyl)-2-pyridinamine; 4-[3-(3-chlorophenyl)-1H-pyrazol-4-yl]-N-ethyl-2-pyridinamine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinecarboxamide; Methyl 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinecarboxylate; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-methyl-2-pyridinecarboxamide; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinecarboxylic acid; 4-[3-(3-fluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(1,3-benzodioxol-5-yl)-1H-pyrazol-4-yl]pyridine; 4-[3-(3-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(1,3-benzodioxol-5-y)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-methylpyridine; 4-[5-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-methylpyridine; 4-[3-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[5-(3-chlorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 2-methyl-4-[1-methyl-3-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 2-methyl-4-[1-methyl-5-(3-methylphenyl)-1H-pyrazol-4-yl]pyridine; 4-(3-phenyl-1H-pyrazol-4-yl)pyridine; 4-[3-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]pyridine; 4-[1-methyl-3-[3-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]pyridine; 4-[3-(3,4-difluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]-2-fluoropyridine; 4-[3-(4-bromophenyl)-1H-pyrazol-4yl]pyridine; 4-[3-(3,4-difluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-bromophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; (E)-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-(2-phenylethenyl)pyridine; (S)-4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]-N-(2-methylbutyl)-2-pyridinamine; 4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]-N-[(4-methoxyphenyl)methyl]-2-pyridinamine; N-[4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-2-pyridinemethanamine; N-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-2-pyridinemethanamine; 2-fluoro-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-iodophenyl)-1H-pyrazol-4-yl]pyridine; 4-[3-(4-iodophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[1-methyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]pyridine; N-[1-(4-fluorophenyl)ethyl]-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinamine; N-[(3-fluorophenyl)methyl]-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinamine; 4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-(1-methylhydrazino)pyridine; 2-fluoro-4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(3,4-difluorophenyl)-1H-pyrazol-4-yl]-2-fluoropyridine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-3-methylpyridine; 4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-3-methylpyridine; 4-[3-(3,4-difluorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-fluoropyridine; 3-(4-fluorophenyl)-N,N-dimethyl-4-(4-pyridinyl)-1H-pyrazole-1-ethanamine; 2-[2-(4-fluorophenyl)ethyl]-4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-[1-(phenylmethyl)-4-piperidinyl]-2-pyridinamine; N′-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-N,N-dimethyl-1,2-ethanediamine; 2,4-bis[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine; N-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-4-morpholineethanamine; 3-(4-fluorophenyl)-4-(2-fluoro-4-pyridinyl)-1H-pyrazole-1-ethanol; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-[2-(1H-imidazol-1-yl)ethyl]-2-pyridinamine; 4-[2-[3-(4-fluorophenyl)-4-(2-fluoro-4-pyridinyl)-1H-pyrazol-1-yl]ethyl]morpholine; (E)-3-(4-fluorophenyl)-4-[2-[2-(4-fluorophenyl)ethenyl]-4-pyridinyl]-1H-pyrazole-1-ethanol; 3-(4-fluorophenyl)-4-(2-fluoro-4-pyridinyl)-N,N-dimethyl-1H-pyrazole-1-ethanamine; 3-(4-fluorophenyl)-4-[2-[2-(4-fluorophenyl)ethyl]-4-pyridinyl]-1H-pyrazole-1-ethanol; 4-[1-[2-(dimethylamino)ethyl]-3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N,N-dimethyl-2-pyridinamine; 4-[1-[2-(dimethylamino)ethyl]-3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-[(4-fluorophenyl)methyl]-2-pyridinamine; 3-(4-fluorophenyl)-4-[2-[2-(4-fluorophenyl)ethyl]-4-pyridinyl]-N,N-dimethyl-1H-pyrazole-1-ethanamine; N-[(4-fluorophenyl)methyl]-4-[3(or 5)-(4-fluorophenyl)-1-[[2-(4-morpholinyl)ethyl]-1H-pyrazol-4-yl]-2-pyridinamine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-4-piperadinyl-2-pyridinamine; N,N-diethyl-3-(4-fluorophenyl)-4-(2-fluoro-4-pyridinyl)-1H-pyrazole-1-ethanamine; 4-[1-[2-(diethylamino)ethyl]-3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-[(4-fluorophenyl)methyl]-2-pyridinamine; 2-[[4-[3-(4-(fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]amino]ethanol; 2-[[4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-pyridinyl]amino]ethanol; 3-[[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]amino]-1-propanol; 3-(4-fluorophenyl)-4-[2-[[(4-fluorophenyl)methyl]amino]-4-pyridinyl]-1H-pyrazole-1-ethanol; 5-(4-fluorophenyl)-4-[2-[[(4-fluorophenyl)methyl]amino]-4-pyridinyl]-1H-pyrazole-1-ethanol; N,N-diethyl-3-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-1-ethanamine; N-[(4-fluorophenyl)methyl]-4-[3-(4-fluorophenyl)-1-[2-(4-morpholinyl)ethyl]-1H-pyrazol-4-yl]-2-pyridinamine; N-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-morpholinepropanamine; N′-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-N,N-dimethyl-1,3-propanediamine; 5-(4-fluorophenyl)-N-2-propynyl-4-(4-pyridinyl)-1H-pyrazol-3-amine; 3-(4-fluorophenyl)-4-[2-[[(4-fluorophenyl)methyl]amino]-4-pyridinyl]-1H-pyrazole-1-ethanol; 5-(4-fluorophenyl)-4-[2-[[(4-fluorophenyl)methyl]amino]-4-pyridinyl]-1H-pyrazole-1-ethanol; 4-[3-[(4-fluorophenyl)-1H-pyrazol-4-yl]quinoline; N-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]glycine methyl ester; N-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]glycine; 4-[3-(4-fluorophenyl)-1-(2-propynyl)-1H-pyrazol-4-yl]pyridine; 4-[5-(4-fluorophenyl)-1-(2-propynyl)-1H-pyrazol-4-yl]pyridine; 4,4′-(1H-pyrazole-3,4-diyl)bis[pyridine]; 4-[3-(3,4-dichlorophenyl)-1H-pyrazol-4-yl]pyridine; N-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-piperidinamine; 2-Chloro-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyrimidine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2(1H)-pyrimidinone hydrazone; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N,N-dimethyl-2-pyrimidinamine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-methyl-2-pyrimidinamine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-(phenylmethyl)-2-pyrimidinamine; N-cyclopropyl-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyrimidinamine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-N-[(4-methoxyphenyl)methyl]-2-pyrimidinamine; 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyrimidinamine; N-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyrimidinyl]-N-(phenylmethyl)acetamide; Ethyl[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyrimidinyl]carbamate; 4-[3-(3-methylphenyl)-1H-pyrazol-4-yl]pyrimidine; 4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]pyrimidine; 4-[3-(3-fluorophenyl)-1H-pyrazol-4-yl]pyrimidine; and 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyrimidine.
- 70. A compound of claim 1 selected from compounds, their tautomers and their pharmaceutically acceptable salts, of the group consisting of
- 71. A compound of claim 1 that is 4-[5-(4-fluorophenyl)-1-(2-propynyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 72. A compound of claim 1 that is 4-[3-(4-fluorophenyl)-1-(2-propynyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 73. A compound of claim 1 that is 3-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-1-ethanol or a pharmaceutically-acceptable salt or a tautomer thereof.
- 74. A compound of claim 1 that is 4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-(1-methylhydrazino)pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 75. A compound of claim 1 that is 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]piperazine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 76. A compound of claim 1 that is 4-[3-cyclopropyl-5-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 77. A compound of claim 1 that is 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 78. A compound of claim 1 that is 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-methylpiperazine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 79. A compound of claim 1 that is 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyrimidine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 80. A compound of claim 1 that is 2-fluoro-4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 81. A compound of claim 1 that is 4-[3-(3,4-diflurophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 82. A compound of claim 1 that is 4-[3-(4-bromophenyl)-1H-pyrazol-4yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 83. A compound of claim 1 that is 4-[3-(4-chlorophenyl)1H-pyrazol-4-yl]-2-fluoropyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 84. A compound of claim 1 that is 4-[3-(1,3-benzodioxol 5-y)-1-methyl-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 85. A compound of claim 1 that is 4-[3-(3-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 86. A compound of claim 1 that is 4-[3-(3-fluorophenyl)-1-methyl-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 87. A compound of claim 1 that is 5-(4-fluorophenyl)-N-2-propynyl-4-(4-pyridinyl)-1H-pyrazol-3-amine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 88. A substituted pyrazole that specifically binds to an ATP binding site of p38 kinase.
- 89. A compound of claim 88 having the formula:
- 90. A compound of claim 89 wherein R2 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical that binds with Lys52, Glu69, Leu73, Ile82, Leu84, Leu101, and Thr103 sidechains at said ATP binding site of p38 kinase, said radical being substantially disposed within a hydrophobic cavity formed during said binding by p38 kinase at the ATP binding site.
- 91. A compound of claim 89 wherein R3 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical having a hydrogen bond acceptor functionality that hydrogen bonds with the N—H backbone of Met106 of p38 kinase.
- 92. A compound of claim 89 wherein R1 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical having a molecular weight less than about 250 atomic mass units.
- 93. A compound of claim 89 wherein R4 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical having a molecular weight less than about 250 atomic mass units.
- 94. A compound of claim 89 wherein
R1 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical having a molecular weight less than about 360 atomic mass units; and R2 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical wherein said radical binds with Lys52, Glu69, Leu73, Ile82, Leu84, Leu101, and Thr103 sidechains at said ATP binding site of p38 kinase, said radical being substantially disposed within a hydrophobic cavity formed during said binding by p38 kinase at the ATP binding site; and R3 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical having a hydrogen bond acceptor functionality that hydrogen bonds with the N—H backbone of Met106 of p38 kinase; and R4 is a hydrocarbyl, heterosubstituted hydrocarbyl or heterocyclyl radical having a molecular weight less than about 360 atomic mass units.
- 95. A compound of claim 94 wherein R1 and R4 are independently selected from hydrocarbyl, heterosubstituted hydrocarbyl and heterocyclyl radicals and have a combined molecular weight less than about 360 atomic mass units.
- 96. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claims 1; or a pharmaceutically acceptable salt thereof.
- 97. A pharmaceutical composition of claim 96 wherein said compound is selected from the compounds of claim 3; or a pharmaceutically acceptable salt thereof.
- 98. A pharmaceutical composition of claim 96 wherein said compound is selected from the compounds of claim 4; or a pharmaceutically acceptable salt thereof.
- 99. A pharmaceutical composition of claim 96 wherein said compound is selected from the compounds of claim 5; or a pharmaceutically acceptable salt thereof.
- 100. A pharmaceutical composition of claim 96 wherein said compound is selected from the compounds of claim 6; or a pharmaceutically acceptable salt thereof.
- 101. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 24; or a pharmaceutically acceptable salt thereof.
- 102. A pharmaceutical composition of claim 101 wherein said compound is selected from the compounds of claim 25; or a pharmaceutically acceptable salt thereof.
- 103. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 25; or a pharmaceutically acceptable salt thereof.
- 104. A pharmaceutical composition of claim 103 wherein said compound is selected from the compounds of claim 36; or a pharmaceutically acceptable salt thereof.
- 105. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 44; or a pharmaceutically acceptable salt thereof.
- 106. A pharmaceutical composition of claim 105 wherein said compound is selected from the compounds of claim 45; or a pharmaceutically acceptable salt thereof.
- 107. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 53; or a pharmaceutically acceptable salt thereof.
- 108. A pharmaceutical composition of claim 107 wherein said compound is selected from the compounds of claim 54; or a pharmaceutically acceptable salt thereof.
- 109. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the of compounds of claim 66; or a pharmaceutically acceptable salt thereof.
- 110. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claims 69; or a pharmaceutically salt thereof.
- 111. A pharmaceutical composition of claim 110 wherein said compound is 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 112. A method of treating a TNF mediated disorder, said method comprising treating the subject having or susceptible to such disorder with a therapeutically-effective amount of a compound of Formula I
- 113. A method of treating a p38 kinase mediated disorder, said method comprising treating the subject having or susceptible to such disorder with a therapeutically-effective amount of a compound of Formula I
- 114. A method of treating inflammation, said method comprising treating the subject having or susceptible to inflammation with a therapeutically-effective amount of a compound of Formula I
- 115. A method of treating arthritis, said method comprising treating the subject having or susceptible to arthritis with a therapeutically-effective amount of a compound of Formula I
- 116. A method of treating a p38 kinase mediated disorder, said method comprising treating the subject having or susceptible to such disorder with a therapeutically-effective amount of a compound of Formula I
- 117. The method of claim 112 wherein the TNF mediated disorder is selected from the group of disorders consisting of bone resorption, graft vs. host reaction, atherosclerosis, arthritis, osteoarthritis, rheumatoid arthritis, gout, psoriasis, topical inflammatory disease state, adult respiratory distress syndrome, asthma, chronic pulmonary inflammatory disease, cardiac reperfusion injury, renal reperfusion injury, thrombus, glomerulonephritis, Crohn's disease, ulcerative colitis, inflammatory bowel disease and cachexia.
- 118. The method of claim 112 wherein the TNF mediated disorder is inflammation.
- 119. The method of claim 112 wherein the TNF mediated disease is arthritis.
- 120. The method of claim 112 wherein the TNF mediated disorder is asthma.
- 121. The method of claim 112 wherein the compound is 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 122. The method of claim 112 wherein the compound is 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-methylpiperazine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 123. The method of claim 113 wherein the disorder is a p38α kinase mediated disorder.
- 124. The method of claim 113 wherein the p38 kinase mediated disorder is selected from the group of disorders consisting of bone resorption, graft vs. host reaction, atherosclerosis, arthritis, osteoarthritis, rheumatoid arthritis, gout, psoriasis, topical inflammatory disease state, adult respiratory distress syndrome, asthma, chronic pulmonary inflammatory disease, cardiac reperfusion injury, renal reperfusion injury, thrombus, glomerulonephritis, Crohn's disease, ulcerative colitis, inflammatory bowel disease and cachexia.
- 125. The method of claim 113 wherein the p38 kinase mediated disorder is inflammation.
- 126. The method of claim 113 wherein the p38 kinase mediated disorder is arthritis.
- 127. The method of claim 113 wherein the p38 kinase mediated disorder is asthma.
- 128. The method of claim 116 wherein the disorder is a p38α kinase mediated disorder.
- 129. The method of claim 116 wherein the p38 kinase mediated disorder is selected from the group of disorders consisting of bone resorption, graft vs. host reaction, atherosclerosis, arthritis, osteoarthritis, rheumatoid arthritis, gout, psoriasis, topical inflammatory disease state, adult respiratory distress syndrome, asthma, chronic pulmonary inflammatory disease, cardiac reperfusion injury, renal reperfusion injury, thrombus, glomerulonephritis, Crohn's disease, ulcerative colitis, inflammatory bowel disease and cachexia.
- 130. The method of claim 116 wherein the p38 kinase mediated disorder is inflammation.
- 131. The method of claim 116 wherein the p38 kinase mediated disorder is arthritis.
- 132. The method of claim 116 wherein the p38 kinase mediated disorder is asthma.
- 133. A method of preparing pyrazoles of Formula I
- 134. The process of claim 133 wherein the acyl hydrazone is formed by reaction of a ketone with an acyl hydrazide.
- 135. The process of claim 133 wherein the condensation is performed at a temperature from about 25° C. to about 200° C.
- 136. A method of preparing pyrazoles of Formula I
- 137. The process of claim 136 wherein it is carried out in an acidic solvent.
- 138. The process of claim 137 wherein the acidic solvent is acetic acid.
- 139. The process of claim 137 wherein the acidic solvent is an organic solvent containing an acid.
- 140. A compound of Formula IA.
- 141. A compound of claim 140 that is 5-(N-acetyl-4-piperidyl)-4-(4-pyridyl)-3-(4-fluorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 142. A compound of claim 140 that is 5-(N-methylsulfonyl-4-piperidyl)-4-(4-pyridyl)-3-(4-fluorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 143. A compound of claim 140 that is 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl)-4-cyclopropylpiperazine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 144. A compound of claim 140 that is 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-methylpiperazine, dihydrate or a pharmaceutically-acceptable salt or a tautomer thereof.
- 145. A compound of claim 140 that is 5-(N-methyl-4-piperidyl)-4-(4-pyridyl)-3-(4-fluorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 146. A compound of claim 140 that is 1-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-4-methylpiperazine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 147. A compound of claim 140 that is 5-(N-methyl-4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 148. A compound of claim 140 that is N-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1-methyl-4-piperidinamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 149. A compound of claim 140 that is 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-piperidinol or a pharmaceutically-acceptable salt or a tautomer thereof.
- 150. A compound of claim 140 that is 5-cis-(4-aminocyclohexyl)-4-(4-pyridyl)-3-(4-fluorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 151. A compound of claim 140 that is 5-(N-methyl-3-piperidyl)-4-(4-pyridyl)-3-(4-fluorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 152. A compound of claim 140 that is N1,N1-diethyl-N4-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-1,4-pentanediamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 153. A compound of claim 140 that is N,N-diethyl-N′-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-1,2-ethanediamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 154. A compound of claim 140 that is 5-(4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 155. A compound of claim 140 that is N4-[4-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]-N1,N1-diethyl-1,4-pentanediamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 156. A compound of claim 140 that is (2R)-1-[[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]amino]-2-propanol or a pharmaceutically-acceptable salt or a tautomer thereof.
- 157. A compound of claim 140 that is N1,N1-diethyl-N4-[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyrimidinyl]-1,4-pentanediamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 158. A compound of claim 140 that is 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-piperidinamine, trihydrochloride or a pharmaceutically-acceptable salt or a tautomer thereof.
- 159. A compound of claim 140 that is N,N-diethyl-N′-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1,3-propanediamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 160. A compound of claim 140 that is 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-N,N-dimethyl-4-piperidinamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 161. A compound of claim 140 that is 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-N,N-dimethyl-4-piperidinamine, trihydrochloride or a pharmaceutically-acceptable salt or a tautomer thereof.
- 162. A compound of claim 140 that is N1,N1-diethyl-N4-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1,4-pentanediamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 163. A compound of claim 140 that is 5-(N-methoxyacetyl-4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 164. A compound of claim 140 that is 5-(N-methylsulfonyl-4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 165. A compound of claim 140 that is 5-cis-(4-aminocyclohexyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 166. A compound of claim 140 that is 5-cis-(4-N,N-dimethylaminocyclohexyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 167. A compound of claim 140 that is 5-[cis-4-N-(2-propyl)aminocyclohexyl]-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 168. A compound of claim 140 that is 5-(N-acetyl-4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 169. A compound of claim 140 that is N-[5-(4-fluorophenyl)-4-(pyridinyl)-1H-pyrazol-3-yl]-1-methyl-4-piperidinamine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 170. A compound of claim 140 that is trans-4-[[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]amino]cyclohexanol or a pharmaceutically-acceptable salt or a tautomer thereof.
- 171. A compound of claim 140 that is 4-[[4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-2-pyridinyl]amino]cyclohexanone or a pharmaceutically-acceptable salt or a tautomer thereof.
- 172. A compound of claim 140 that is 5-(N-methyl-4-piperidyl)-4-(4-pyrimidyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 173. A compound of claim 140 that is 5-(N-methoxyethyl-4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 174. A compound of claim 140 that is 3-(4-chlorophenyl)-5-[(1-methylpiperidin-4-yl)-oxy]-4-pyridin-4-yl-1H-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 175. A compound of claim 140 that is 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-3-methylpiperazine or a pharmaceutically-acceptable salt or a tautomer thereof.
- 176. A compound of claim 140 that is 1-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-N,N-diethyl-4-piperidinamine, trihydrochloride or a pharmaceutically-acceptable salt or a tautomer thereof.
- 177. A compound of claim 140 that is 3-(4-chlorophenyl)-5-[(1-methylpiperidin-4-yl)-thio]-4-pyridin-4-yl-1H-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 178. A compound of claim 140 that is 3-(4-chlorophenyl)-5-[(piperidin-4-yl)-thio]-4-pyridin-4-yl-1H-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 179. A compound of claim 140 that is 3-(4-chlorophenyl)-5-[(2-methoxyethyl)-thio]-4-pyridin-4-yl-1H-pyrazole or a pharmaceutically-acceptable salt or a tautomer thereof.
- 180. A compound of claim 140 that is [3-(4-chlorophenyl)-4-pyridin-4-yl-1H-pyrazole-5-yl]thio]-acetonitrile or a pharmaceutically-acceptable salt or a tautomer thereof.
- 181. A pharmaceutical composition comprising a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 140; or a pharmaceutically acceptable salt thereof.
- 182. A method of treating inflammation, said method comprising treating the subject having or susceptible to inflammation with a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 140; or a pharmaceutically acceptable salt thereof.
- 183. A method of treating arthritis, said method comprising treating the subject having or susceptible to arthritis with a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 140; or a pharmaceutically acceptable salt thereof.
- 184. A method of treating a p38 kinase mediated disorder, said method comprising treating the subject having or susceptible to such disorder with a therapeutically-effective amount of a compound, said compound selected from the compounds of claim 140; or a pharmaceutically acceptable salt thereof.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority from U.S. Provisional Application Serial No. 60/047,570 filed May 22, 1997. This application also is a continuation-in-part application of U.S. application Ser. No. 09/083,670 filed May 22, 1998.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60047570 |
May 1997 |
US |
Divisions (3)
|
Number |
Date |
Country |
| Parent |
10114297 |
Apr 2002 |
US |
| Child |
10374781 |
Feb 2003 |
US |
| Parent |
09918481 |
Jul 2001 |
US |
| Child |
10114297 |
Apr 2002 |
US |
| Parent |
09196623 |
Nov 1998 |
US |
| Child |
09918481 |
Jul 2001 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
| Parent |
09083670 |
May 1998 |
US |
| Child |
09196623 |
Nov 1998 |
US |
Patent Application
20040176433
