| Sonstiges: |
- Nachgewiesen in: USPTO Patent Grants
- Sprachen: English
- Patent Number: 9,090,593
- Publication Date: July 28, 2015
- Appl. No: 13/991603
- Application Filed: December 07, 2011
- Assignees: AMGEN INC. (Thousand Oaks, CA, US)
- Claim: 1. A compound of Formula 1a [chemical expression included] wherein X 1 is CH or N; wherein X 2 is CH or N; wherein X 3 is C or N; wherein R is substituted or unsubstituted aryl, substituted or unsubstituted 5-membered heterocyclyl, substituted or unsubstituted 6-membered heterocyclyl, substituted or unsubstituted 9 membered heterocyclyl, substituted or unsubstituted 10 membered heterocyclyl, cycloalkylalkenyl, 1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyranyl], alkylcarbonylamino, phenylaminocarbonyl, phenylcarbonylamino, benzylaminocarbonyl, alkylcarbonyl, hydroxyalkyl, haloalkyl, cyanoalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted arylamino, alkenyl, or haloalkenyl; wherein R 1 is [chemical expression included] and wherein R g is H or F; wherein R 1A is H, hydroxy, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 5-6-membered heterocyclyl-amino, substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino, substituted or unsubstituted 5-6-membered heterocyclyloxy, alkylamino, C 3 -C 6 cycloalkylamino, substituted or unsubstituted 5-6-membered heterocyclyl-S—, substituted or unsubstituted phenylamino or 9-10 membered nitrogen containing heterocyclyl; wherein R 1B is H, hydroxy or C 1 -C 3 -alkoxy; wherein R 1C is H, hydroxy, C 1 -C 3 -alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, or substituted or unsubstituted 5-6-membered heterocyclyl-amino; wherein R 1E is H, hydroxy, C 1 -C 3 -alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 5-6-membered heterocyclyl-amino, substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino, substituted or unsubstituted 5-6-membered heterocyclyloxy or alkylamino; wherein R 1F is H, or substituted or unsubstituted 6-membered heterocyclyl; wherein R 1G is H, hydroxy or C 1 -C 3 -alkoxy; wherein R 1J is H, hydroxy, C 1 -C 3 -alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, or substituted or unsubstituted 5-6-membered heterocyclyl-amino or substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino or substituted or unsubstituted 5-6-membered heterocyclyloxy or alkylamino or substituted or unsubstituted 5-6-membered heterocyclyl-S—, or substituted or unsubstituted phenyl or 9-10 membered nitrogen containing heterocyclyl; wherein R 1H is H, hydroxy or C 1 -C 3 -alkoxy; wherein R 1M is H, lower alkyl, lower alkoxy, lower alkylamino, lower dialkylamino, substituted or unsubstituted 5-6-membered heterocyclyloxy, substituted or unsubstituted 5-6-membered heterocyclyl or substituted or unsubstituted 5-6-membered heterocyclylamino; wherein R 1N is H, or C 1 -C 3 -alkoxy; and wherein R 1P substituted or unsubstituted phenylamino, lower alkylamino, substituted or unsubstituted 5-membered nitrogen-containing heterocyclyl, substituted or unsubstituted 5-membered nitrogen-containing heterocyclylamino, substituted or unsubstituted 6-membered nitrogen-containing heterocyclylamino, or substituted or unsubstituted 6-membered nitrogen-containing heterocyclyl; or a pharmaceutically acceptable salt thereof; provided R 1 is not 4-pyridyl when R is 3-pyridyl, when X 1 is CH, X 2 is CH and X 3 is C; further provided R is not 2,6-dimethyl-3,5-dicyano-dihydropyridyl when X 1 is N, X 2 is CH and X 3 is C; further provided R 1 is not 2-(4-morpholinyl-4-phenylamino)-4-pyrimidyl when X 1 is CH, X 2 is CH and X 3 is C; further provided R is not 2-(3-furyl)-(5-phenyl-2-aminopropoxy)-3-pyridyl when X 1 is N, X 2 is CH and X 3 is C; further provided R is not triazolyl or tetrazolyl when X 1 is N, X 2 is CH and X 3 is C; further provided R is not 7,9-dicyano-[1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazin-8-yl when X 1 is N, X 2 is CH and X 3 is C; further provided R is not 2-methoxypyridyl when Ry is 2-(4-amino-1-piperidyl)-6-pyrazinyl; and further provided R is not 3-cyano-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-4-yl when X 1 is N, X 2 is CH, X 3 is C, R g is H and R 1 is 2-isopropoxypyridin-5-yl.
- Claim: 2. The compound of claim 1 wherein X 1 is CH; wherein X 2 is CH; wherein X 3 is C; and wherein R g is H; or a pharmaceutically acceptable salt thereof.
- Claim: 3. The compound of claim 1 wherein X 1 is N; wherein X 2 is CH; wherein X 3 is C; and wherein R g is H; or a pharmaceutically acceptable salt thereof.
- Claim: 4. The compound of claim 1 wherein X 1 is CH; wherein X 2 is N; wherein X 3 is C; and wherein R g is H; or a pharmaceutically acceptable salt thereof.
- Claim: 5. The compound of claim 1 wherein R is C 1-4 hydroxyalkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 3 -C 6 -cycloalkyl-C 2 -C 3 -alkenyl, C 1-4 alkylcarbonyl, C 1-4 alkylcarbonylamino, phenylaminocarbonyl, phenylcarbonylamino, benzylaminocarbonyl, substituted or unsubstituted C 6 -C 10 -arylamino, C 2-4 alkenyl, or C 2-4 haloalkenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 6. The compound of claim 1 wherein R is methylcarbonyl, cyanomethyl, 2,6-difluorophenylamino, ethylcarbonylamino, phenylcarbonylamino, phenylaminocarbonyl, benzylaminocarbonyl, hydroxyethyl, 1-hydroxy-2-propyl, isopropyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, 3,3,3-trifluoroprop-2-yl, prop-1-en-2-yl, 3,3,3-trifluoroprop-1-en-2-yl or cyclopropylethenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 7. The compound of claim 1 wherein R is substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted phenyl or substituted or unsubstituted 5-membered heterocyclyl or substituted or unsubstituted 6-membered heteroaryl or substituted or unsubstituted 9 membered heteroaryl or substituted or unsubstituted 10 membered heteroaryl; or a pharmaceutically acceptable salt thereof.
- Claim: 8. The compound of claim 1 wherein R is substituted or unsubstituted phenyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyranyl, substituted or unsubstituted 5,6-dihydro-2H-pyranyl, substituted or unsubstituted 3,6-dihydro-2H-pyranyl, substituted or unsubstituted tetrahydro-pyranyl, substituted or unsubstituted morpholinyl, substituted or unsubstituted imidazolidinyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted cyclopentyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyridyl, substituted or unsubstituted indazolyl, substituted or unsubstituted quinoxalinyl, substituted or unsubstituted 1H-pyrazolo[3,4-b]pyridinyl, substituted or unsubstituted 2,3-dihydro-indolyl, substituted or unsubstituted benzothiazolyl, substituted or unsubstituted 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, substituted or unsubstituted 3,4-dihydro-2H-1,4-benzoxazinyl, substituted or unsubstituted 1H-pyrrolo[2,3-b]pyridinyl, substituted or unsubstituted 1H-pyrrolo[3,2-c]pyridinyl, substituted or unsubstituted imidazo[1,2-a]pyrazinyl, substituted or unsubstituted [1,2,4]triazolo[4,3-a]pyridinyl, substituted or unsubstituted 1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]yl, substituted or unsubstituted 2,3-dihydro-1,4-benzodioxinyl, or substituted or unsubstituted quinolyl; or a pharmaceutically acceptable salt thereof.
- Claim: 9. The compound of claim 1 wherein R is phenyl, 2,6-difluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 2,3-difluorophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-fluoro-5-nitrophenyl, 4-aminocarbonyl-2-fluorophenyl, 3-aminocarbonyl-6-fluorophenyl, 2-fluoro-5-isopropylaminocarbonylphenyl, 2-fluoro-5-cyclopropylaminocarbonylphenyl, 2-fluoro-5-phenylaminocarbonylphenyl, 2-fluoro-3-diethylaminocarbonylphenyl, 2-fluoro-5-diethylaminocarbonylphenyl, 2-fluoro-5-dimethylaminocarbonylphenyl, 2-fluoro-5-benzylaminocarbonylphenyl, 2-fluoro-5-tert-butylaminocarbonylphenyl, 2-fluoro-5-butylaminocarbonylphenyl, 2-fluoro-5-propylaminocarbonylphenyl, 2-fluoro-5-ethylaminocarbonylphenyl, 3-cyclopropylaminocarbonylphenyl, 3-cyclopropylaminocarbonyl-6-fluorophenyl, 2-fluoro-5-cyclohexylaminocarbonylphenyl, 2-fluoro-5-(piperidin-1-ylcarbonyl)phenyl, 2-fluoro-5-(morpholin-4-ylcarbonyl)phenyl, 2-fluoro-3-methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-fluoro-4-hydroxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 3,5-dimethoxyphenyl, 3-isopropoxyphenyl, 3-trifluoromethoxyphenyl, 2-trifluoromethylphenyl, 3-aminophenyl, 3-amino-2-methylphenyl, 3-(1-hydroxyethyl)phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyano-2-fluorophenyl, 2-cyano-6-fluorophenyl, 2-chlorophenyl, 2-chloro-6-fluorophenyl, 3-chloro-6-fluorophenyl, 4-chloro-2-fluorophenyl, 3-methylsulfonylphenyl, 2-fluoro-4-methylsulfonylphenyl, 4-methylsulfonylphenyl, 2,6-difluoro-4-methylsulfonylphenyl, 2-fluoro-4-methylsulfonylamino-phenyl, 4-aminosulfonyl-2-fluorophenyl, 3-dimethylaminophenyl, 3-amino-4-morpholinophenyl, 3-amino-6-trifluoromethoxyphenyl, 4-amino-2-fluorophenyl, 2-fluoro 4-methylcarbonylamino-phenyl, ethynylphenyl, (1-chlorovinyl)benzene, 2-methylphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-hydroxy-3-pyridyl, 2-amino-4-pyridyl, 3-amino-5-pyridyl, 3-amino-2-pyridyl, 2-amino-6-fluoro-5-pyridyl, 4-cyano-3-pyridyl, 2-cyano-3-pyridyl, 2-cyclopropyl-6-pyridyl, 4-cyclopropyl-2-pyridyl, 2-fluoro-5-methoxy-4-pyridyl, 5-fluoro-2-methoxy-4-pyridyl, 3-chloro-6-fluoro-5-pyridyl, 2-methoxy-6-pyridyl, 2-methoxy-4-pyridyl, 3-methoxy-5-pyridyl, 2,3-dimethoxy-5-pyridyl, 3-isopropoxy-5-pyridyl, 2-isopropoxy-4-pyridyl, 2-isopropoxy-6-pyridyl, 2-isopropoxy-5-chloro-6-pyridyl, 2-ethoxy-6-pyridyl, 2-fluoro-6-pyridyl, 2-fluoro-3-pyridyl, 4-fluoro-3-pyridyl, 2,4-difluoro-3-pyridyl, 3-fluoro-2-pyridyl, 3-fluoro-4-pyridyl, 3-fluoro-5-pyridyl, 3-methyl-2-pyridyl, 2-trifluoromethyl-6-pyridyl, 4-trifluoromethyl-2-pyridyl, 3-chloro-2-pyridyl, 2-tert-butylaminocarbonyl-6-pyridyl, 4-cyclopropylaminocarbonyl-2-pyridyl, 3-cyclopropylaminocarbonyl-5-pyridyl, 3-chloro-6-oxo-pyrid-4-yl, 4-isopropyl-2-pyrimidinyl, pyrimidin-5-yl, 2-amino-pyrimidin-5-yl, 2-hydroxypyrimidin-4-yl, 2-methoxypyrimidin-4-yl, 2,4-dimethoxy-pyrimidin-6-yl, 2-cyclopropylpyrimidin-6-yl, 2-(4-morpholinyl)-pyrimidin-4-yl, 4-(3-methylmorpholin-4-yl)-pyrimidin-2-yl, 2-amino-4-cyclopentylamino-pyrimidin-5-yl, 4-cyclopropylaminopyrimidin-2-yl, 4-isobuthylpyrimidin-2-yl, 4-cyclopropylpyrimidin-2-yl, 2-cyclopropylpyrimidin-4-yl, 4-oxo-pyrimidin-5-yl, 2-methoxy-pyrimidin-4-yl, 2-isopropoxypyrimidin-4-yl, 3-pyrazinyl, 2-aminopyrazin-6-yl, 2-cyclopropyl-6-pyrazinyl, 2-cyclopropylamino-6-pyrazinyl, 2-isopropoxy-6-pyrazinyl, 3-pyridazinyl, 4-amino-pyridazin-6-yl, 3-quinolyl, 2-hydroxy-3-quinolyl, 2-chloro-3-quinolyl, 7-methoxy-4-quinolyl, 7-fluoro-4-quinolyl, 7-cyano-4-quinolyl, 7-trifluoromethoxy-4-quinolyl, 2-methoxy-3-quinolyl, 1-methyl-2-oxo-quinolin-4-yl, 1-methyl-2-oxo-isoquinolin-6-yl, 6-quinoxalinyl, 3-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl, 3-trifluoromethyl-5-indazolyl, 1-methyl-2-oxo-2,3-dihydro-indol-5-yl, 1-(2-aminopyrimidin-4-yl)-2,3-dihydro-indol-6-yl, benzothiazol-5-yl, benzothiazol-6-yl, 4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl, 4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl, 1H-pyrrolo[2,3-b]pyridin-5-yl, 1H-pyrrolo[3,2-c]pyridin-4-yl, 1H-pyrrolo[3,2-c]pyridin-6-yl, 1H-pyrrolo[2,3-b]pyridin-6-yl, imidazo[1,2-a]pyrazin-5-yl, [1,2,4]triazolo[4,3-a]pyridin-5-yl, 1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]-4-yl and 2,3-dihydro-1,4-benzodioxin-6-yl, 1H-pyrazol-5-yl, 1-methyl-1H-pyrazol-4-yl, 1-methyl-1H-pyrazol-5-yl, 1-isopropyl-1H-pyrazol-4-yl, thiazol-2-yl, 2-(2-methylpiperidin-1-yl)thiazol-4-yl, 2-(pyrrolidin-1-yl)thiazol-4-yl, 1-methyl-5-imidazolyl, 2-oxazolyl, 4-pyranyl, 3-pyranyl, 5,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl, tetrahydro-4-pyranyl, tetrahydro-3-pyranyl, 2-oxo-pyrrolidin-1-yl, 2-oxo-piperidin-1-yl, morpholin-4-yl, 1-methyl-2-oxo-imidazolidin-3-yl, 1-piperidinyl, cyclopropyl, cyclobutyl, cyclopentyl, 3-methyl-morpholin-4-yl, 2-methyl-morpholin-4-yl, 3-oxo-morpholin-4-yl, morpholin-4-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 10. The compound of claim 1 wherein R 1A is piperidin-3-ylamino, piperidin-4-ylamino, piperidin-4-yl-N-methylamino, piperidin-3-yl-N-methylamino, pyrrolidin-3-ylamino, 3-azetidinylamino, cyclopropylamino, hydroxy, methoxy, isopropoxy, trifluoroethoxy, fluoroethoxy, 3-pyridyloxy, 3-azetidinyloxy, pyrrolidin-3-yloxy, piperidin-3-yloxy, 4-fluoro-piperidin-3-yloxy, 3-fluoro-piperidin-4-yloxy, 3-fluoro-piperidin-5-yloxy, 3-methyl-piperidin-3-yloxy, 3-methyl-piperidin-5-yloxy, 1-methyl-piperidin-4-yloxy, 4-isopropyl-piperidin-3-yloxy, 4-ethyl-piperidin-3-yloxy, 4-methyl-piperidin-3-yloxy, 4,4-dimethyl-piperidin-3-yloxy, 3,3-dimethyl-piperidin-4-yloxy, piperidin-4-yloxy, 1,2,3,6-tetrahydro-3-pyridinyloxy, 6-azaspiro[2.5]oct-4-yloxy, 5-azaspiro[2.5]oct-8-yloxy, 3-azabicyclo[4.1.0]hept-5-yloxy, ((3S)-4-methylidene-3-piperidinyl)oxy, piperidin-3-ylthio, methylamino, ethylamino, isopropylamino, tert-butylamino, dimethylamino, phenylamino, piperidin-3-ylmethyl, piperidin-4-ylmethyl, cyclopropyl, 3-pyridyl, 5-indazolyl, 1,4-diazepan-1-yl, 1-pyrrolidinyl, 3-hydroxypyrrolidin-1-yl, 3,4-dihydroxypyrrolidin-1-yl, 3-aminopyrrolidinyl, 4-aminopiperidin-1-yl, 3-aminopiperidinyl, 3-hydroxypiperidin-1-yl, 3,4-dihydroxypiperidin-1-yl, 4-hydroxypiperidinyl, 4-morpholinyl, 3-pyrazolyl, 3-azetidinyl, 1-piperazinyl, or 1-piperidinyl; R 1E is 4-aminopiperidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino, piperidin-4-yloxy or piperidin-3-yl; R 1G is H, hydroxy or methoxy; R 1H is H, hydroxy or methoxy; R 1J is 4-aminopiperidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino or piperidin-3-yl; R 1M is butyl, dimethylamino, isopropylamino, isopropoxy, 3-fluoro-piperidin-4-yloxy, 4-fluoro-piperidin-3-yloxy, piperidin-3-yloxy, 6-azaspiro[2.5]octan-4-yloxy, 4-aminopiperidin-1-yl, 3-hydroxypyrrolidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino or 3-methylpiperidin-5-ylamino; wherein R 1N is H or methoxy; and wherein R 1P phenylamino, isopropylamino, 3-aminopiperidin-1-yl, 4-aminopiperidin-1-yl, piperidin-3-ylamino, pyrrolidin-3-ylamino, or pyrrolidin-1-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 11. A compound of Formula 2′ [chemical expression included] Wherein R z is substituted or unsubstituted thiazolyl, substituted or unsubstituted oxadiazolyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted oxo-pyrimidinyl or substituted or unsubstituted indazolyl; Wherein R is substituted or unsubstituted cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 7-azaindolyl, substituted or unsubstituted 1,2,3,4-tetrahydro-1,8-naphthyridyl, substituted or unsubstituted 1H-pyrazolo[3,4-b]pyridyl, substituted or unsubstituted benzomorpholinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyridyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted pyrazolyl, or substituted or unsubstituted oxazolyl; or a pharmaceutically acceptable salt thereof; provided R z is not 4-pyridyl when R is 3-pyridyl.
- Claim: 12. The compound of claim 11 wherein R z is substituted or unsubstituted thiazol-4-yl or substituted or unsubstituted oxadiazol-2-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 13. The compound of claim 11 wherein R is substituted or unsubstituted phenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 14. The compound of claim 11 wherein R is substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted pyrimidinyl, or substituted or unsubstituted pyridyl, or a pharmaceutically acceptable salt thereof.
- Claim: 15. The compound of claim 11 wherein R z is 2-(1-imidazolyl)thiazol-4-yl, 2-(2-oxo-pyrid-1-yl)thiazol-4-yl, 5-isopropylamino-oxadiazol-2-yl, 5-phenylamino-oxadiazol-2-yl, 5-(3-aminopiperidin-1-yl)oxadiazol-2-yl, 5-(4-aminopiperidin-1-yl)oxadiazol-2-yl, 5-(piperidin-3-ylamino)oxadiazol-2-yl, 5-(pyrrolidin-3-ylamino)oxadiazol-2-yl, 5-pyrrolidin-1-yl-oxadiazol-2-yl, pyrazin-2-yl, 2-dimethylaminopyrazin-6-yl, 2-(cyclohexylamino)pyrazin-6-yl, 2-(pyrrolidin-3-ylamino)pyrazin-6-yl, 2-(piperidin-3-ylamino)pyrazin-6-yl, 2-(piperidin-4-ylamino)pyrazin-6-yl, 2-(2-oxopiperazin-4-ylamino)pyrazin-6-yl, 2-(piperidin-3-yloxy)pyrazin-6-yl, 2-(3-amino-pyrrolidin-1-yl)pyrazin-6-yl, 2-(4-aminopiperidin-1-yl)pyrazin-6-yl, 2-isopropylaminopyrazin-6-yl, 2-(3-aminopiperidin-1-yl)pyrazin-6-yl, 2-(morpholin-4-yl)pyrazin-6-yl, 2-methoxy-pyrazin-6-yl, 2-methoxy-pyrazin-5-yl, 2-isopropoxy-pyrazin-6-yl, 2-(piperidin-3-yloxy)pyrazin-6-yl, 2-(piperidin-4-yloxy)pyrazin-6-yl, 2-cyclopropylpyrazin-6-yl, 2-(morpholin-4-yl)pyrid-6-yl, 2-(2-oxo-pyrrolidin-1-yl)pyrid-6-yl, 2-(pyrazol-1-yl)pyrid-6-yl, 3-fluoro-6-pyridyl, 2-amino-6-pyridyl, 2-amino-4-pyridyl, 4-amino-2-pyridyl, 2-amino-3-chloropyrid-5-yl, 4-methyl-2-pyridyl, 3-methyl-6-pyridyl, 2-isopropoxy-pyrid-6-yl, 4-(piperidin-3-ylamino)pyrimidin-2-yl, 4-(piperidin-3-ylamino)-6-methoxypyrimidin-2-yl, 2-(4-aminopiperidin-1-yl)-4-methoxypyrimidin-6-yl, 2-(4-aminopiperidin-1-yl)-4-oxypyrimidin-6-yl, 4-(piperidin-3-yloxy)pyrimidin-2-yl, 4-(piperidin-4-yloxy)pyrimidin-2-yl, 4-(piperidin-4-ylamino)pyrimidin-2-yl, 4-(piperidin-3-ylamino)-6-hydroxypyrimidin-2-yl, 2-(piperidin-3-ylamino)-6-hydroxypyrimidin-4-yl, 2-(morpholinin-4-yl)-6-hydroxypyrimidin-4-yl, 2-(morpholinin-4-yl)-4-hydroxypyrimidin-6-yl, 2-(morpholinin-4-yl)-4-methoxypyrimidin-6-yl, 4-(morpholinin-4-yl)-6-methoxypyrimidin-2-yl, 2-(piperidin-3-yloxy)-6-methoxypyrimidin-4-yl, 2-(piperidin-3-ylamino)-6-methoxypyrimidin-4-yl, 2-(4-aminopiperidin-1-yl)-4-methoxypyrimidin-6-yl, 2-(4-aminopiperidin-1-yl)-4-hydroxypyrimidin-6-yl, 4-(4-aminopiperidin-1-yl)-6-hydroxypyrimidin-2-yl, 4-cyclopropylpyrimidin-2-yl, 6-(4-aminopiperidin-1-yl)-2-oxopyrimidin-4-yl, 2-(4-aminopiperidin-1-yl)-4-oxopyrimidin-6-yl, 2-isopropylamino-4-oxopyrimidin-6-yl, 4-isopropylamino-2-oxopyrimidin-6-yl, 2-dimethylamino-4-oxopyrimidin-6-yl, 4-dimethylamino-6-oxopyrimidin-2-yl, or 6-indazolyl; or a pharmaceutically acceptable salt thereof.
- Claim: 16. The compound of claim 11 wherein R is phenyl, 2-fluorophenyl, 2,6-difluorophenyl, 2-chloro-6-fluorophenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-4-cyanophenyl, 4-fluoro-3-cyanophenyl, 3-chloro-6-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2,5-dimethoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-cyano-5,6-dimethoxyphenyl, 3-cyano-4-isopropoxyphenyl, 4-isopropoxyphenyl, 3-isopropoxyphenyl, 3-cyano-5-methoxy-6-propoxyphenyl, 3-cyano-6-isopropoxy 5-methoxyphenyl, 2-cyano-5-isopropoxy-4-methoxyphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 2,3-dimethylphenyl, 3,5-dimethyl-4-methoxyphenyl, 3-hydroxymethylphenyl, 4-hydroxymethylphenyl, 3-(2-hydroxyethyl)phenyl, 2-methyl-5-trifluoromethylphenyl, 3-carboxyphenyl, 2-cyanophenyl, 4-(methylcarbonylamino)phenyl, 4-(cyclopropylcarbonylamino)phenyl, 3-(cyclobutylaminocarbonyl)-6-methylphenyl, 3-(methylcarbonylamino)-5-trifluoromethylphenyl, 3-(ethylaminocarbonyl)-6-methylphenyl, 3-difluoromethoxyphenyl, 4-amino-3-trifluoromethoxyphenyl, benzodioxolyl, 3-(pyrazol-3-yl)phenyl, 3-tetrazol-5-ylphenyl, 3-isoxazol-5-ylphenyl, 3-(2-methylthiazol-4-yl)phenyl, 3-(1-cyanocyclobutyl)phenyl, or 4-(morpholin-4-yl)phenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 17. The compound of claim 11 wherein R z is thiazol-4-yl substituted with substituted or unsubstituted 5-membered nitrogen-containing heterocyclyl or substituted or unsubstituted 6-membered nitrogen-containing heterocyclyl, oxadiazol-2-yl substituted with phenylamino, lower alkylamino, 5-membered nitrogen-containing heterocyclyl, substituted or unsubstituted 5-membered nitrogen-containing heterocyclylamino, substituted or unsubstituted 6-membered nitrogen-containing heterocyclylamino, or substituted or unsubstituted 6-membered nitrogen-containing heterocyclyl, pyrazin-2-yl substituted with alkylamino, dialkylamino, lower cycloalkylamino, substituted or unsubstituted 5-membered nitrogen-containing heterocyclyl, substituted or unsubstituted 6-membered nitrogen-containing heterocyclyl, C 1 -C 3 alkoxy, substituted or unsubstituted 6-membered nitrogen-containing heterocyclyloxy, substituted or unsubstituted 6-membered nitrogen-containing heterocyclylamino, substituted or unsubstituted 5-membered nitrogen-containing heterocyclylamino, substituted or unsubstituted C 3 -C 6 cycloalkyl, pyrid-2-yl substituted with substituted or unsubstituted 5-membered nitrogen-containing heterocyclyl, substituted or unsubstituted 6-membered nitrogen-containing heterocyclyl, C 1 -C 3 alkoxy, C 1 -C 3 alkyl, amino, fluoro, pyrid-4-yl substituted with amino, pyrimidin-2-yl substituted with substituted or unsubstituted 6-membered nitrogen-containing heterocyclyloxy, or substituted or unsubstituted 6-membered nitrogen-containing heterocyclylamino, 2-oxo-pyrimidin-4-yl unsubstituted or substituted with substituted or unsubstituted 6-membered nitrogen-containing heterocyclyloxy, or substituted or unsubstituted 6-membered nitrogen-containing heterocyclylamino, or substituted or unsubstituted indazolyl; wherein the substituted 5-membered nitrogen-containing heterocyclyl, or substituted 6-membered nitrogen-containing heterocyclyl are substituted with one or more substituents selected from hydroxy, amino, oxo, methyl, fluoro, ═CH 2 , or a pharmaceutically acceptable salt thereof.
- Claim: 18. The compound of claim 11 wherein R is oxazolyl, 1-cyclopropyl-3-pyrazolyl, 2-(2-methylpiperidin-1-yl)thiazol-4-yl, or 1-isopropylpyrazol-4-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 19. The compound of claim 11 wherein R is 2-(isopropoxy)-pyrazin-6-yl, 2-cyclopentyloxypyrazin-6-yl, 2-cyclopropylpyrazin-6-yl, 2-cyclopropylaminopyrazin-6-yl, 2-dimethylamino-pyrazin-5-yl, 2-isopropoxypyrazin-6-yl, 2-(pyrazol-1-yl)pyrazin-5-yl, 2-(pyrrolidin-1-yl)pyrazin-6-yl, 2-(3-methylpiperidin-1-yl)pyrazin-5-yl, 3-chloropyrid-5-yl, 3-chloropyrid-4-yl, 3-cyclopropylaminopyrid-5-yl, 3-fluoro-6-methoxypyrid-4-yl, 2-methoxypyrid-3-yl, 2-methoxypyrid-5-yl, 2-cyclopentyloxy-pyrid-6-yl, 2-cyclobutyloxy-pyrid-6-yl, 2-cyclopropylmethoxy-pyrid-5-yl, 2-(piperazin-1-yl)pyrid-6-yl, 2-(4-methylpiperidin-1-yl)-6-pyridyl, 2-(2-methyl-imidazol-1-yl)pyrid-6-yl, 2-(3-methylpyrazol-1-yl)pyrid-6-yl, 3-(pyrrolidin-2-yl)pyrid-5-yl, 2-cyanopyrid-3-yl, 2-chloro-3-methylsulfonylamino-pyrid-5-yl, 2-(4-aminophenyloxy)pyrid-3-yl, 2-(morpholin-4-yl)pyrid-3-yl, 4-dihydroxypyrimidin-5-yl, or 4-cyclopropylpyrimidin-2-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 20. The compound of claim 11 wherein R is 2,2-dimethylcyclopropyl; or a pharmaceutically acceptable salt thereof.
- Claim: 21. The compound of claim 11 wherein R is 3-methyl-1H-pyrazolo[3,4-b]pyrid-5-yl, 7-azaindol-5-yl, 4-methylbenzomorpholin-7-yl, or 1,2,3,4-tetrahydro-1,8-naphthyrid-6-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 22. A compound of Formula 3′ [chemical expression included] Wherein R g is H or F; Wherein R y is [chemical expression included] Wherein R is substituted or unsubstituted C 6 -C 10 -aryl, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 9-10-membered heterocyclyl, 1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]-4-yl, halo, C 1-4 hydroxyalkyl, C 1-4 haloalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, C 3 -C 6 -cycloalkyl-C 2 -C 3 -alkenyl, C 1-4 alkylcarbonyl, C 1-4 alkylcarbonylamino, phenylaminocarbonyl, phenylcarbonylamino, C 1-4 cyanoalkyl, benzylaminocarbonyl, substituted or unsubstituted C 6 -C 10 -arylamino, C 2-4 alkenyl, or C 2-4 haloalkenyl; provided R is not 2-methoxypyridyl when Ry is 2-(4-amino-1-piperidyl)-6-pyrazinyl; Wherein R 1A is H, hydroxy, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 5-6-membered heterocyclyl-amino, substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino, substituted or unsubstituted 5-6-membered heterocyclyloxy, alkylamino, C 3 -C 6 cycloalkylamino, substituted or unsubstituted 5-6-membered heterocyclyl-S—, or substituted or unsubstituted phenylamino or 9-10 membered nitrogen containing heterocyclyl; Wherein R 1C is H, C 1 -C 3 -alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, or substituted or unsubstituted 5-6-membered heterocyclyl-amino; Wherein R 1E is H, C 1 -C 3 -alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, substituted or unsubstituted 5-6-membered heterocyclyl-amino, substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino, substituted or unsubstituted 5-6-membered heterocyclyloxy or alkylamino; Wherein R 1F is H, or substituted or unsubstituted 6-membered heterocyclyl; Wherein R 1G is H, hydroxy or C 1 -C 3 -alkoxy; Wherein R 1H is H, hydroxy or C 1 -C 3 -alkoxy; Wherein R 1J is H, hydroxy, C 1 -C 3 -alkoxy, substituted or unsubstituted 5-6-membered heterocyclyl, or substituted or unsubstituted 5-6-membered heterocyclyl-amino, or substituted or unsubstituted 5-6-membered heterocyclyl-(alkyl)amino or substituted or unsubstituted 5-6-membered heterocyclyloxy or alkylamino or substituted or unsubstituted 5-6-membered heterocyclyl-S—, or substituted or unsubstituted phenyl or 9-10 membered nitrogen containing heterocyclyl; and Wherein R 1M is H, lower alkyl, lower alkoxy, lower alkylamino, lower dialkylamino, substituted or unsubstituted 5-6-membered heterocyclyloxy, substituted or unsubstituted 5-6-membered heterocyclyl or substituted or unsubstituted 5-6-membered heterocyclylamino; or a pharmaceutically acceptable salt thereof; provided R is not 2,6-dimethyl-3,5-dicyano-dihydropyridyl; further provided R is not 2-(3-furyl)-(5-phenyl-2-aminopropoxy)-3-pyridyl; further provided R is not triazolyl or tetrazolyl; further provided R is not 7,9-dicyano-[1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazin-8-yl; and further provided R is not 3-cyano-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridin-4-yl, when R g is H and R 1 is 2-isopropoxypyridin-5-yl.
- Claim: 23. The compound of claim 22 wherein R 1A is piperidin-3-ylamino, piperidin-4-ylamino, piperidin-4-yl-N-methylamino, piperidin-3-yl-N-methylamino, pyrrolidin-3-ylamino, 3-azetidinylamino, cyclopropylamino, hydroxy, methoxy, isopropoxy, trifluoroethoxy, fluoroethoxy, 3-pyridyloxy, 3-azetidinyloxy, pyrrolidin-3-yloxy, piperidin-3-yloxy, 4-fluoro-piperidin-3-yloxy, 3-fluoro-piperidin-4-yloxy, 3-fluoro-piperidin-5-yloxy, 3-methyl-piperidin-3-yloxy, 3-methyl-piperidin-5-yloxy, 1-methyl-piperidin-4-yloxy, 4-isopropyl-piperidin-3-yloxy, 4-ethyl-piperidin-3-yloxy, 4-methyl-piperidin-3-yloxy, 4,4-dimethyl-piperidin-3-yloxy, 3,3-dimethyl-piperidin-4-yloxy, piperidin-4-yloxy, 1,2,3,6-tetrahydro-3-pyridinyloxy, 6-azaspiro[2.5]oct-4-yloxy, 5-azaspiro[2.5]oct-8-yloxy, 3-azabicyclo[4.1.0]hept-5-yloxy, ((3S)-4-methylidene-3-piperidinyl)oxy, piperidin-3-ylthio, methylamino, ethylamino, isopropylamino, tert-butylamino, dimethylamino, phenylamino, piperidin-3-ylmethyl, piperidin-4-ylmethyl, cyclopropyl, 3-pyridyl, 5-indazolyl, 1,4-diazepan-1-yl, 1-pyrrolidinyl, 3-hydroxypyrrolidin-1-yl, 3,4-dihydroxypyrrolidin-1-yl, 3-aminopyrrolidinyl, 4-aminopiperidin-1-yl, 3-aminopiperidinyl, 3-hydroxypiperidin-1-yl, 3,4-dihydroxypiperidin-1-yl, 4-hydroxypiperidinyl, 4-morpholinyl, 3-pyrazolyl, 3-azetidinyl, 1-piperazinyl, or 1-piperidinyl; R 1E is 4-aminopiperidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino, piperidin-4-yloxy or piperidin-3-yl; R 1G is H, hydroxy or methoxy; R 1H is H, hydroxy or methoxy; R 1J is 4-aminopiperidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino or piperidin-3-yl; and R 1M is butyl, dimethylamino, isopropylamino, isopropoxy, 3-fluoro-piperidin-4-yloxy, 4-fluoro-piperidin-3-yloxy, piperidin-3-yloxy, 6-azaspiro[2.5]octan-4-yloxy, 4-aminopiperidin-1-yl, 3-hydroxypyrrolidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino or 3-methylpiperidin-5-ylamino; or a pharmaceutically acceptable salt thereof.
- Claim: 24. The compound of claim 22 wherein R is substituted or unsubstituted Nitrogen containing-6 membered heteroaryl or substituted or unsubstituted phenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 25. The compound of claim 22 wherein R is phenyl substituted or unsubstituted with one or more substituents selected from fluoro, chloro, nitro, amino, cyano, methyl, trifluoromethyl, 1-hydroxyethyl, ethynyl, 1-chlorovinyl, oxo, hydroxy, methoxy, isopropoxy, trifluoromethoxy, methylsulfonyl, dimethylamino, morpholinyl, aminosulfonyl, methylsulfonylamino, aminocarbonyl, methylcarbonylamino, isopropylaminocarbonyl, cyclopropylaminocarbonyl, phenylaminocarbonyl, diethylaminocarbonyl, dimethylaminocarbonyl, benzylaminocarbonyl, tert-butylaminocarbonyl, butylaminocarbonyl, propylaminocarbonyl, ethylaminocarbonyl, cyclopropylaminocarbonyl, cyclohexylaminocarbonyl, piperidinylcarbonyl or morpholinylcarbonyl; or a pharmaceutically acceptable salt thereof.
- Claim: 26. The compound of claim 22 wherein R is pyridyl, or pyrimidinyl, or pyrazinyl, or pyridazinyl, wherein R is substituted or unsubstituted with one or more substituents selected from hydroxy, amino, cyano, cyclopropyl, fluoro, chloro, methoxy, isopropoxy, ethoxy, methyl, isopropyl, isobutyltrifluoromethyl, tert-butylaminocarbonyl, tert-butylcarbonylamino, 4-cyclopropylaminocarbonyl, oxo, morpholinyl, 3-methylmorpholinyl, cyclopropylamino or cyclopentylamino; and a pharmaceutically acceptable salt thereof.
- Claim: 27. The compound of claim 22 wherein R is quinolyl, isoquinolinyl, quinoxalinyl, pyrazolo[3,4-b]pyridinyl, 2,3-dihydro-indolyl, indazolyl, benzothiazolyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[3,2-c]pyridinyl, imidazo[1,2-a]pyrazinyl, [1,2,4]triazolo[4,3-a]pyridinyl, 1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyranyl] or 2,3-dihydro-1,4-benzodioxinyl; wherein R is substituted or unsubstituted with one or more substituents selected from hydroxy, cyano, chloro, methoxy, fluoro, trifluoromethoxy, methyl, oxo, trifluoromethyl or 2-aminopyrimidin-4-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 28. The compound of claim 22 wherein R is cyclopropyl, cyclobutyl, cyclopentyl, pyranyl, 5,6-dihydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholinyl, or imidazolidinyl; wherein R is substituted or unsubstituted with one or more substituents selected from methyl, or oxo; or a pharmaceutically acceptable salt thereof.
- Claim: 29. The compound of claim 22 wherein R is methylcarbonyl, cyanomethyl, 2,6-difluorophenylamino, ethylcarbonylamino, phenylcarbonylamino, phenylaminocarbonyl, benzylaminocarbonyl, hydroxyethyl, 1-hydroxy-2-propyl, isopropyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, 3,3,3-trifluoroprop-2-yl, prop-1-en-2-yl, 3,3,3-trifluoroprop-1-en-2-yl or cyclopropylethenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 30. The compound of claim 22 wherein R is phenyl, 2,6-difluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 2,3-difluorophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-fluoro-5-nitrophenyl, 4-aminocarbonyl-2-fluorophenyl, 3-aminocarbonyl-6-fluorophenyl, 2-fluoro-5-isopropylaminocarbonylphenyl, 2-fluoro-5-cyclopropylaminocarbonylphenyl, 2-fluoro-5-phenylaminocarbonylphenyl, 2-fluoro-3-diethylaminocarbonylphenyl, 2-fluoro-5-diethylaminocarbonylphenyl, 2-fluoro-5-dimethylaminocarbonylphenyl, 2-fluoro-5-benzylaminocarbonylphenyl, 2-fluoro-5-tert-butylaminocarbonylphenyl, 2-fluoro-5-butylaminocarbonylphenyl, 2-fluoro-5-propylaminocarbonylphenyl, 2-fluoro-5-ethylaminocarbonylphenyl, 3-cyclopropylaminocarbonylphenyl, 3-cyclopropylaminocarbonyl-6-fluorophenyl, 2-fluoro-5-cyclohexylaminocarbonylphenyl, 2-fluoro-5-(piperidin-1-ylcarbonyl)phenyl, 2-fluoro-5-(morpholin-4-ylcarbonyl)phenyl, 2-fluoro-3-methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-fluoro-4-hydroxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 3,5-dimethoxyphenyl, 3-isopropoxyphenyl, 3-trifluoromethoxyphenyl, 2-trifluoromethylphenyl, 3-aminophenyl, 3-amino-2-methylphenyl, 3-(1-hydroxyethyl)phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyano-2-fluorophenyl, 2-cyano-6-fluorophenyl, 2-chlorophenyl, 2-chloro-6-fluorophenyl, 3-chloro-6-fluorophenyl, 4-chloro-2-fluorophenyl, 3-methylsulfonylphenyl, 2-fluoro-4-methylsulfonylphenyl, 4-methylsulfonylphenyl, 2,6-difluoro-4-methylsulfonylphenyl, 2-fluoro-4-methylsulfonylamino-phenyl, 4-aminosulfonyl-2-fluorophenyl, 3-dimethylaminophenyl, 3-amino-4-morpholinophenyl, 3-amino-6-trifluoromethoxyphenyl, 4-amino-2-fluorophenyl, 2-fluoro 4-methylcarbonylamino-phenyl, ethynylphenyl, (1-chlorovinyl)benzene, 2-methylphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-hydroxy-3-pyridyl, 2-amino-4-pyridyl, 3-amino-5-pyridyl, 3-amino-2-pyridyl, 2-cyclopropyl-6-pyridyl, 4-cyclopropyl-2-pyridyl, 2-fluoro-5-methoxy-4-pyridyl, 5-fluoro-2-methoxy-4-pyridyl, 3-chloro-6-fluoro-5-pyridyl, 2-methoxy-6-pyridyl, 2-methoxy-4-pyridyl, 3-methoxy-5-pyridyl, 2,3-dimethoxy-5-pyridyl, 3-isopropoxy-5-pyridyl, 2-isopropoxy-4-pyridyl, 2-isopropoxy-6-pyridyl, 2-isopropoxy-5-chloro-6-pyridyl, 2-ethoxy-6-pyridyl, 2-fluoro-6-pyridyl, 3-fluoro-2-pyridyl, 3-fluoro-5-pyridyl, 3-methyl-2-pyridyl, 2-trifluoromethyl-6-pyridyl, 3-chloro-2-pyridyl, 2-tert-butylaminocarbonyl-6-pyridyl, 4-cyclopropylaminocarbonyl-2-pyridyl, 3-cyclopropylaminocarbonyl-5-pyridyl, 3-chloro-6-oxo-pyrid-4-yl, 4-isopropyl-2-pyrimidinyl, pyrimidin-5-yl, 2-amino-pyrimidin-5-yl, 2-hydroxypyrimidin-4-yl, 2-methoxypyrimidin-4-yl, 2,4-dimethoxy-pyrimidin-6-yl, 2-cyclopropylpyrimidin-6-yl, 2-(4-morpholinyl)-pyrimidin-4-yl, 2-amino-4-cyclopentylamino-pyrimidin-5-yl, 4-cyclopropylpyrimidin-2-yl, 4-oxo-pyrimidin-5-yl, 2-methoxy-pyrimidin-4-yl, 2-isopropoxypyrimidin-4-yl, 3-pyrazinyl, 2-cyclopropyl-6-pyrazinyl, 2-cyclopropylamino-6-pyrazinyl, 2-isopropoxy-6-pyrazinyl, 3-pyridazinyl, 4-amino-pyridazin-6-yl, 3-quinolyl, 2-hydroxy-3-quinolyl, 2-chloro-3-quinolyl, 7-methoxy-4-quinolyl, 7-fluoro-4-quinolyl, 7-cyano-4-quinolyl, 7-trifluoromethoxy-4-quinolyl, 2-methoxy-3-quinolyl, 1-methyl-2-oxo-quinolin-4-yl, 1-methyl-2-oxo-isoquinolin-6-yl, 6-quinoxalinyl, 3-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl, 3-trifluoromethyl-5-indazolyl, 1-methyl-2-oxo-2,3-dihydro-indol-5-yl, 1-(2-aminopyrimidin-4-yl)-2,3-dihydro-indol-6-yl, benzothiazol-5-yl, benzothiazol-6-yl, 4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl, 4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl, 1H-pyrrolo[2,3-b]pyridin-5-yl, 1H-pyrrolo[2,3-b]pyridin-6-yl, imidazo[1,2-a]pyrazin-5-yl, [1,2,4]triazolo[4,3-a]pyridin-5-yl, 1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]-4-yl and 2,3-dihydro-1,4-benzodioxin-6-yl, 1H-pyrazol-5-yl, 1-methyl-1H-pyrazol-4-yl, thiazol-2-yl, 2-(2-methylpiperidin-1-yl)thiazol-4-yl, 2-(pyrrolidin-1-yl)thiazol-4-yl, 4-pyranyl, 3-pyranyl, 5,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl, tetrahydro-4-pyranyl, tetrahydro-3-pyranyl, 2-oxo-pyrrolidin-1-yl, 2-oxo-piperidin-1-yl, morpholin-4-yl, 1-methyl-2-oxo-imidazolidin-3-yl, 1-piperidinyl, phenylaminocarbonyl, benzylaminocarbonyl, or cyclopropylethenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 31. The compound of claim 22 wherein R 1E is H, hydroxy, methoxy, piperidin-3-yloxy, isopropylamino, 4-amino-piperidin-1-yl, methylamino, piperidin-3-ylamino, piperidin-4-ylamino, 4-aminopiperidin-1-yl, piperidin-4-yloxy or piperidin-3-yl; wherein R 1G is H, hydroxy, or methoxy; or a pharmaceutically acceptable salt thereof.
- Claim: 32. The compound of claim 22 wherein R 1A is piperidin-3-ylamino, piperidin-4-ylamino, piperidin-4-yl-N-methylamino, piperidin-3-yl-N-methylamino, pyrrolidin-3-ylamino, 3-azetidinylamino, cyclopropylamino, hydroxy, methoxy, isopropoxy, trifluoroethoxy, fluoroethoxy, 3-pyridyloxy, 3-azetidinyloxy, pyrrolidin-3-yloxy, piperidin-3-yloxy, 4-fluoro-piperidin-3-yloxy, 3-fluoro-piperidin-4-yloxy, 3-fluoro-piperidin-5-yloxy, 3-methyl-piperidin-3-yloxy, 3-methyl-piperidin-5-yloxy, 1-methyl-piperidin-4-yloxy, 4-isopropyl-piperidin-3-yloxy, 4-ethyl-piperidin-3-yloxy, 4-methyl-piperidin-3-yloxy, 4,4-dimethyl-piperidin-3-yloxy, 3,3-dimethyl-piperidin-4-yloxy, piperidin-4-yloxy, 1,2,3,6-tetrahydro-3-pyridinyloxy, 6-azaspiro[2.5]oct-4-yloxy, 5-azaspiro[2.5]oct-8-yloxy, 3-azabicyclo[4.1.0]hept-5-yloxy, ((3S)-4-methylidene-3-piperidinyl)oxy, piperidin-3-ylthio, methylamino, ethylamino, isopropylamino, tert-butylamino, dimethylamino, phenylamino, piperidin-3-ylmethyl, piperidin-4-ylmethyl, cyclopropyl, 3-pyridyl, 5-indazolyl, 1,4-diazepan-1-yl, 1-pyrrolidinyl, 3-hydroxypyrrolidin-1-yl, 3,4-dihydroxypyrrolidin-1-yl, 3-aminopyrrolidinyl, 4-aminopiperidin-1-yl, 3-aminopiperidinyl, 3-hydroxypiperidin-1-yl, 3,4-dihydroxypiperidin-1-yl, 4-hydroxypiperidinyl, 4-morpholinyl, 3-pyrazolyl, 3-azetidinyl, 1-piperazinyl, or 1-piperidinyl; or a pharmaceutically acceptable salt thereof.
- Claim: 33. The compound of claim 22 wherein R 1F is 4-amino-piperidin-1-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 34. The compound of claim 22 wherein R y is [chemical expression included] a pharmaceutically acceptable salt thereof.
- Claim: 35. The compound of claim 22 wherein R 1C is H, hydroxy, methoxy, piperidin-3-ylamino, piperidin-4-ylamino, piperidin-4-yl-N-methylamino, piperidin-3-yl-N-methylamino, pyrrolidin-3-ylamino, 3-azetidinylamino, 3-pyridyl, 1-pyrrolidinyl, 3-hydroxypyrrolidin-1-yl, 3-aminopyrrolidinyl, 4-aminopiperidinyl, 3-aminopiperidinyl, 3-hydroxypiperidin-1-yl, 4-hydroxypiperidinyl, 4-morpholinyl, 3-pyrazolyl, 3-azetidinyl, 1-piperazinyl, or 1-piperidinyl; or a pharmaceutically acceptable salt thereof.
- Claim: 36. The compound of claim 22 wherein R is unsubstituted or substituted 5-membered heteroaryl; or a pharmaceutically acceptable salt thereof.
- Claim: 37. The compound of claim 22 wherein R is unsubstituted or substituted thiazolyl, unsubstituted or substituted imidazolyl, unsubstituted or substituted oxazolyl or unsubstituted or substituted pyrazolyl; or a pharmaceutically acceptable salt thereof.
- Claim: 38. The compound of claim 22 wherein R is pyrazolyl, thiazolyl, imidazolyl, or oxazolyl; wherein R is substituted or unsubstituted with one or more substituents selected from methyl, isopropyl, 2-methylpiperidin-1-yl, pyrrolidin-1-yl or oxo; or a pharmaceutically acceptable salt thereof.
- Claim: 39. The compound of claim 18 wherein R y is; [chemical expression included] or a pharmaceutically acceptable salt thereof.
- Claim: 40. The compound of claim 22 wherein R y is [chemical expression included] wherein R 1C is H, hydroxy, methoxy or 4-aminopiperidin-1-yl; or a pharmaceutically acceptable salt thereof.
- Claim: 41. The compound of claim 22 wherein R y is [chemical expression included] wherein R 1M is butyl, dimethylamino, isopropylamino, isopropoxy, 3-fluoro-piperidin-4-yloxy, 4-fluoro-piperidin-3-yloxy, piperidin-3-yloxy, 6-azaspiro[2.5]octan-4-yloxy, 4-aminopiperidin-1-yl, 3-hydroxypyrrolidin-1-yl, piperidin-3-ylamino, piperidin-4-ylamino or 3-methylpiperidin-5-ylamino; or a pharmaceutically acceptable salt thereof.
- Claim: 42. A compound of Formula 4′ [chemical expression included] Wherein R x is [chemical expression included] Wherein R is substituted or unsubstituted phenyl or substituted or unsubstituted 5-membered heteroaryl, or substituted or unsubstituted 6-membered heteroaryl; Wherein R 1A is H, methoxy, substituted or unsubstituted 6-membered heterocyclyl-amino or substituted or unsubstituted 6-membered heterocyclyl; Wherein R 1B is H or methoxy; Wherein R 1C is H, methoxy, substituted or unsubstituted 6-membered heterocyclyl, or substituted or unsubstituted 6-membered heterocyclyl-amino; Wherein R 1M is H, methoxy or substituted or unsubstituted 6-membered heterocyclyl; and Wherein R 1N is H or methoxy; and or a pharmaceutically acceptable salt thereof.
- Claim: 43. The compound of claim 42 wherein R is substituted or unsubstituted phenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 44. The compound of claim 42 wherein R is 2-fluorophenyl, or 2,6-difluorophenyl; or a pharmaceutically acceptable salt thereof.
- Claim: 45. The compound of claim 42 wherein R x is [chemical expression included] or a pharmaceutically acceptable salt thereof.
- Claim: 46. The compound of claim 42 wherein R 1A is H, methoxy, piperid-3-ylamino or 4-amino-piperidyl; wherein R 1B is H or methoxy; or a pharmaceutically acceptable salt thereof.
- Claim: 47. The compound of claim 42 wherein R x is [chemical expression included] or a pharmaceutically acceptable salt thereof.
- Claim: 48. The compound of claim 42 wherein R 1C is piperid-3-ylamino or 4-amino-piperidyl; or a pharmaceutically acceptable salt thereof.
- Claim: 49. A composition comprising a therapeutically effective amount of compound of claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.
- Claim: 50. A method for treating a cancer disorder in a patient, comprising administering to the patient a composition comprising an amount of a compound of claim 1 wherein the cancer is multiple myeloma or Non Hodgkins Lymphoma, or AML.
- Claim: 51. A compound of claim 1 selected from 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(4-piperidinyloxy)-2-pyrazinyl)-1H-indazole; 6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-N-(1-methylethyl)-2-pyrazinamine; N-cyclopropyl-6-(3-(6-methoxy-2-pyrazinyl)-1H-indazol-5-yl)-2-pyrazinamine; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3R,4S)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3S,4R)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3R,4R)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3S,4S)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 6-(3-(6-(4-amino-1-piperidinyl)-2-pyrazinyl)-1H-indazol-5-yl)-N-cyclopropyl-2-pyrazinamine; 6-(3-(6-(2-fluoroethoxy)-2-pyrazinyl)-1H-indazol-5-yl)-2-pyrazinamine; 1-(6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-2-pyrazinyl)-4-piperidinamine; 6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-N-4-piperidinyl-2-pyrazinamine; 6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-N-((3R)-3-piperidinyl)-2-pyrazinamine; (4-(3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indol-5-yl)phenyl)methanol; 1-(6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indol-3-yl)-2-pyrazinyl)-4-piperidinamine; 5-(4-(4-morpholinyl)phenyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 3-(6-((8R)-5-azaspiro[2.5]oct-8-yloxy)-2-pyrazinyl)-5-(6-cyclopropyl-2-pyrazinyl)-1H-indazole; 5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 5-(1-(1-methylethyl)-1H-pyrazol-4-yl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 5-(3-fluoro-4-pyridinyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 3,5-bis(6-cyclopropyl-2-pyrazinyl)-1H-indazole; 1-(6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indol-3-yl)-2-pyrazinyl)-4-piperidinamine; 3-(6-((4R)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(3,6-dihydro-2H-pyran-4-yl)-1H-indazole; 3-(6-((4R)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(2,6-difluorophenyl)-1H-indole; 3-(6-((4S)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(2,6-difluorophenyl)-1H-indole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(4-piperidinyloxy)-2-pyrazinyl)-1H-indazole; 6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-N-(1-methylethyl)-2-pyrazinamine; N-cyclopropyl-6-(3-(6-methoxy-2-pyrazinyl)-1H-indazol-5-yl)-2-pyrazinamine; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3R,4S)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3S,4R)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3R,4R)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 5-(6-cyclopropyl-2-pyrazinyl)-3-(6-(((3S,4S)-3-fluoro-4-piperidinyl)oxy)-2-pyrazinyl)-1H-indazole; 6-(3-(6-(4-amino-1-piperidinyl)-2-pyrazinyl)-1H-indazol-5-yl)-N-cyclopropyl-2-pyrazinamine; 6-(3-(6-(2-fluoroethoxy)-2-pyrazinyl)-1H-indazol-5-yl)-2-pyrazinamine; 1-(6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-2-pyrazinyl)-4-piperidinamine; 6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-N-4-piperidinyl-2-pyrazinamine; 6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-N-((3R)-3-piperidinyl)-2-pyrazinamine; (4-(3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indol-5-yl)phenyl)methanol; N-cyclopropyl-6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indazol-3-yl)-2-pyrazinamine; 5-(4-(4-morpholinyl)phenyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 3-(6-((8R)-5-azaspiro[2.5]oct-8-yloxy)-2-pyrazinyl)-5-(6-cyclopropyl-2-pyrazinyl)-1H-indazole; 5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 5-(1-(1-methylethyl)-1H-pyrazol-4-yl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 5-(3-fluoro-4-pyridinyl)-3-(6-((3R)-3-piperidinyloxy)-2-pyrazinyl)-1H-indole; 1-(6-(5-(6-cyclopropyl-2-pyrazinyl)-1H-indol-3-yl)-2-pyrazinyl)-4-piperidinamine; 3-(6-((4R)-6-azaspiro[25]oct-4-yloxy)-2-pyrazinyl)-5-(3,6-dihydro-2H-pyran-4-yl)-1H-indazole; 3-(6-((4R)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(2,6-difluorophenyl)-1H-indole; 3-(6-((4S)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(2,6-difluorophenyl)-1H-indole; 3-(6-((8R)-5-azaspiro[2.5]oct-8-yloxy)-2-pyrazinyl)-5-(6-cyclopropyl-2-pyrazinyl)-1H-indazole; 3,5-bis(6-cyclopropyl-2-pyrazinyl)-1H-indazole; and 3-(6-((8S)-5-azaspiro[2.5]oct-8-yloxy)-2-pyrazinyl)-5-(6-cyclopropyl-2-pyrazinyl)-1H-indazole; or a pharmaceutically acceptable salt thereof.
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- Primary Examiner: Jackson, Shawquia
- Attorney, Agent or Firm: Friedrichsen, Bernard P.
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