Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors

A method of treating cancer comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of any one of the following Formulae (III) to (VIII):

• or a pharmaceutically acceptable salt thereof, wherein:
• R3 is C1-6 alkyl, Cy, or -L-Cy;
• L is unsubstituted C1-6 alkylene or C1-6 alkylene substituted with 1, 2 or 3 substituents independently selected from F, Cl, CN, OH and O(C1-6 alkyl);
• Cy is unsubstituted or substituted C6-10 aryl, unsubstituted or substituted 5-10 membered heteroaryl, unsubstituted or substituted C3-6 cycloalkyl or unsubstituted or substituted 4-11 membered heterocycloalkyl,
• wherein the substituted C6-10 aryl, 5-10 membered heteroaryl, C3-6 cycloalkyl or 4-11 membered heterocycloalkyl forming Cy is substituted with 1, 2, or 3 substituents each independently selected from halogen, RCy1, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, C1-6 haloalkyl, CN, OH, and C1-6 alkoxy;
• wherein each RCy1 is, independently, C1-6 alkyl, each of which is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, CN, and ORa1;
• and
• wherein Ra1 is independently, at each occurrence, selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl.

A method of treating cancer comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound selected from the following compounds:

• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(2,6-difluorophenyl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-isopropyl-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(tetrahydro-2H-pyran-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(2,6-difluoro-4-methoxyphenyl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(1-ethyl-1H-pyrazol-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-isopropenyl-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(6-methoxypyridin-3-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-morpholin-4-yl-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-isopropylquinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-ylquinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-ylquinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3-oxa-9-azaspiro[5.5]undec-9-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3-oxa-9-azaspiro[5.5]undec-9-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-cyanopiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-cyanopiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-pyridin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-pyridin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-ethyl-3-oxopiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-ethyl-3-oxopiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methoxypiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methoxypiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-morpholin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-morpholin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-[3-(trifluoromethyl)pyrrolidin-1-yl]quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-[3-(trifluoromethyl)pyrrolidin-1-yl]quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-pyrrolidin-1-ylquinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-pyrrolidin-1-ylquinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3,3-dimethylazetidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3,3-dimethylazetidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-azetidin-1-ylquinoline-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(2,6-difluoro-4-methoxyphenyl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(6-methoxypyridin-3-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(6-morpholin-4-ylpyridin-3-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(1-ethyl-1H-pyrazol-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(3-oxa-9-azaspiro[5.5]undec-9-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(4-cyanopiperidin-1-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(1-oxa-8-azaspiro[4.5]dec-8-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(1-ethyl-1H-pyrazol-4-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(6-methoxypyridin-3-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(6-morpholin-4-ylpyridin-3-yl)quinoline-2-carboxamide;
• N-(4-(3-amino-4-hydroxy-5-methylpiperidin-1-yl)pyridin-3-yl)-7-(pyridin-3-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(2-cyanophenyl)quinoline-2-carboxamide;
• N-(4-(3-amino-5-methylpiperidin-1-yl)pyridin-3-yl)-7-(4-hydroxypiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[3-amino-5-(trifluoromethyl)piperidin-1-yl]pyridin-3-yl}-7-(2-cyanophenyl)-1,5-naphthyridine-2-carboxamide;
• and
• N-{4-[3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-[6-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl]quinoline-2-carboxamide,
• or a pharmaceutically acceptable salt thereof.

A method of treating cancer comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound selected from the following compounds:

• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(2,6-difluorophenyl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-isopropyl-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(tetrahydro-2H-pyran-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(2,6-difluoro-4-methoxyphenyl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(1-ethyl-1H-pyrazol-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-isopropenyl-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(6-methoxypyridin-3-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-yl-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-isopropylquinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-ylquinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-ylquinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3-oxa-9-azaspiro[5.5]undec-9-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3-oxa-9-azaspiro[5.5]undec-9-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-cyanopiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-cyanopiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-pyridin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-pyridin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-ethyl-3-oxopiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-ethyl-3-oxopiperazin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methoxypiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-methoxypiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-morpholin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(4-morpholin-4-ylpiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-[3-(trifluoromethyl)pyrrolidin-1-yl]quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-[3-(trifluoromethyl)pyrrolidin-1-yl]quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-pyrrolidin-1-ylquinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-pyrrolidin-1-ylquinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3,3-dimethylazetidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(3,3-dimethylazetidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-azetidin-1-ylquinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl}-7-(2, 6-difluoro-4-methoxyphenyl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(6-methoxypyridin-3-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(6-morpholin-4-ylpyridin-3-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(1-ethyl-1H-pyrazol-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(3-oxa-9-azaspiro[5.5]undec-9-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(4-cyanopiperidin-1-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-5-cyclopropyl-4-hydroxypiperidin-1-yl]pyridin-3-yl)}-7-(1-oxa-8-azaspiro[4.5]dec-8-yl)-1,5-naphthyridine-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl)}-7-(-methyl-1H-pyrazol-4-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(1-ethyl-1H-pyrazol-4-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(6-methoxypyridin-3-yl)quinoline-2-carboxamide;
• N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(6-morpholin-4-ylpyridin-3-yl)quinoline-2-carboxamide;
• N-(4-((3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl)pyridin-3-yl)-7-(pyridin-3-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]pyridin-3-yl}-7-(2-cyanophenyl)quinoline-2-carboxamide;
• N-(4-((3S,5R)-3-amino-5-methylpiperidin-1-yl)pyridin-3-yl)-7-(4-hydroxypiperidin-1-yl)quinoline-2-carboxamide;
• N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]pyridin-3-yl}-7-(2-cyanophenyl)-1,5-naphthyridine-2-carboxamide;
• and
• N-{4-[(3R,4R,5 S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-[6-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl]quinoline-2-carboxamide,
• or a pharmaceutically acceptable salt thereof.