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US 8,710,076 B2Granted
2,5-disubstituted piperidine orexin receptor antagonists
AssigneeMerck Sharp & Dohme Corp.
InventorsMichael J. Breslin, Paul J. Coleman, Christopher D. Cox, Izzat T. Raheem, Anthony J. Roecker, John D. Schreier
Life of this patent
Estimating the term…
Abstract
The present invention is directed to 2,5-disubstituted piperidine amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
Claims7
A compound of the formula Ia:
- wherein:
- B is isoquinoline;
- R1a, R1b and R1c are independently selected from the group consisting of:
- (1) hydrogen,
- (2) halogen,
- (3) C1-6alkyl,
- (4) triazolyl,
- (5) oxazolyl,
- (6) pyrimidinyl, and
- (7) phenyl;
- R2a, R2b and R2c are independently selected from the group consisting of:
- (1) hydrogen,
- (2) halogen,
- (3) C1-6alkyl, which is unsubstituted or substituted with halogen,
- (4) —O—C1-6alkyl, which is unsubstituted or substituted with halogen, and
- (5) —NH—C1-6alkyl, or —N(C1-6alkyl)(C1-6alkyl), which is unsubstituted or substituted with halogen;
- R3 is C1-6alkyl;
- or a pharmaceutically acceptable salt thereof.
15 more elements
A compound which is selected from the group consisting of:
- 1-({6-methyl-1[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)-isoquinoline;
- 1-({(2R,5R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)-isoquinoline;
- 1-({(2S,5R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)-isoquinoline;
- 1-({(2R,5S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)-isoquinoline;
- 1-({(2S,5R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)-isoquinoline;
- N-{6-methyl-1-[5methyl-2(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}isoquinolin-1-amine;
- N-{(2R,5R)-6-methyl-1-[5methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}isoquinolin-1-amine;
- N-{(2S,5S)-6-methyl-1-[5methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}isoquinolin-1-amine;
- N-{(2R,5S)-6-methyl-1-[5methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}isoquinolin-1-amine;
- N-{(2S,5R)-6-methyl-1-[5methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}isoquinolin-1-amine;
- 8-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-8-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-8-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-8-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-8-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 5-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-5-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-5-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-5-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-5-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 1-chloro-4-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-1-chloro-4-({6-methyl-1-[2(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-1-chloro-4-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-1-chloro-4-({6-methyl-1-[2(2H- 1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-1-chloro-4-({6-methyl-1-[2-(2H- 1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 1-({6methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 7-bromo-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-7-bromo-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-7-bromo-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-7-bromo-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-7-bromo-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 4-methoxy-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-4-methoxy-1-({6-methyl-1[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-4-methoxy-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-4-methoxy-1-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-4-methoxy-1-({6-methyl-1-[2-(2H- 1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 1-({6-methyl-1-[methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-1-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-1-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-1-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5R)-1-({6-methyl-1-[5-methyl-2(2H- 1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- 1-{[6-methyl-1-(2-pyridin-3-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2R,5R)-1-{[6-methyl-1-(2-pyridin-3-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2S,5S)-1-{[6-methyl-1-(2-pyridin-3-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2R,5S)-1-{[6-methyl-1-(2-pyridin-3-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2S,5R)-1-{[6-methyl-1-(2-pyridin-3-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- 1-{[6-methyl-1-(2-pyrimidin-2-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2R,5R)-1-{[6-methyl-1-(2-pyrimidin-2-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2S,5S)-1-{[6-methyl-1-(2-pyrimidin-2-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2R,5S)-1-{[6-methyl-1-(2-pyrimidin-2-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- (2S,5R)-1-{[6-methyl-1-(2-pyrimidin-2-ylbenzoyl)piperidin-3-yl]oxy}isoquinoline;
- 1-({6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5R)-1-({6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2S,5S)-1-({6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- (2R,5S)-1-({6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- and
- (2S,5R)-1-({6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}oxy)isoquinoline;
- or a pharmaceutically acceptable salt thereof.
59 more elements
Dependencies are inferred from the claim text.