US 8,569,311 B2Granted

Pyridyl piperidine orexin receptor antagonists

AssigneeMerch Sharp & Dohme Corp.

InventorsMichael J. Breslin, Paul J. Coleman, Christopher D. Cox, John D. Schreier

Life of this patent

Estimating the term…

Abstract

The present invention is directed to pyridyl piperidine 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.

Claims15

Dependent claims

A compound of the formula Ic:

wherein:
R1a, R1b and R1c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) —(C═O)m—On—C1-6alkyl, where m is 0 or 1, n is 0 or 1 (wherein if m is 0 or n is 0, a bond is present) and where the alkyl is unsubstituted or substituted with one or more substituents selected from R13,
(4) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R13,
(5) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R13,
(6) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R13,
(7) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R13,
(8) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R13,
(9) —(C═O)m—NR10R11, wherein R10 and R11 are independently selected from the group consisting of:
(a) hydrogen,
(b) C1-6alkyl, which is unsubstituted or substituted with R13,
(c) C3-6alkenyl, which is unsubstituted or substituted with R13,
(d) C3-6alkynyl, which is unsubstituted or substituted with R13,
(e) C3-6cycloalkyl which is unsubstituted or substituted with R13,
(f) phenyl, which is unsubstituted or substituted with R13, and
(g) heterocycle, which is unsubstituted or substituted with R13,
(10) —S(O)2—NR10R11,
(11) —S(O)qR12, where q is 0, 1 or 2 and where R12 is selected from the definitions of R10 and R11,
(12) —CO2H,
(13) —CN, and
(14) —NO2;
R2a, R2b and R2c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) —(C═O)m—On—C1-6alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R13,
(5) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R13,
(6) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R13,
(7) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R13,
(8) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R13,
(9) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R13,
(10) —(C═O)m—NR10R11,
(11) —S(O)2—NR10R11,
(12) —S(O)q—R12,
(13) —CO2H,
(14) —CN, and
(15) —NO2;
R3 is C1-6alkyl or C3-6cycloalkyl, which is unsubstituted or substituted with one or more substituents selected from R13;
R13 is selected from the group consisting of:
(1) halogen,
(2) hydroxyl,
(3) —(C═O)m—On—C1-6alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R14,
(4) —On—(C1-3)perfluoroalkyl,
(5) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R14,
(6) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R14,
(7) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R14,
(8) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R14,
(9) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R14,
(10) —(C═O)m—NR10R11,
(11) —S(O)2—NR10R11,
(12) —S(O)q—R12,
(13) —CO2H,
(14) —CN, and
(15) —NO2;
R14 is selected from the group consisting of:
(1) hydroxyl,
(2) halogen,
(3) C1-6alkyl,
(4) —C3-6cycloalkyl,
(5) —O—C1-6alkyl,
(6) —O(C═O)—C1-6alkyl,
(7) —NH—C1-6alkyl,
(8) phenyl,
(9) heterocycle,
(10) —CO2H, and
(11) —CN;
or a pharmaceutically acceptable salt thereof.

66 more elements

A compound which is selected from the group consisting of:

5-fluoro-2-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl }methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3S,6S)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6S)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3S,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-{2-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrazine;
2-{2-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrazine;
2-{2-[((2S,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrazine;
2-{2-[(2R,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrazine;
2-{2-[((2S,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrazine;
2-methyl-6-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-methyl-6-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-methyl-6-({(3S,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-methyl-6-({(3R,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-methyl-6-({(3S,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-{2-[(2R,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrimidine;
2-{2-[((2S,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-methylphenyl}pyrimidine;
3-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzoic acid;
3-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzoic acid;
3-[((2S,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzoic acid;
3-[((2R,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzoic acid;
3-[((2S,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)benzoic acid;
[3-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)phenyl]methanol;
[3-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)phenyl]methanol;
[3-[((2S,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)phenyl]methanol;
[3-[((2R,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)phenyl]methanol;
[3-[((2S,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-(2H-1,2,3-triazol-2-yl)phenyl]methanol;
3-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylbenzoic acid;
3-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylbenzoic acid;
3-[((2S,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylbenzoic acid;
3-[((2R,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylbenzoic acid;
3-[((2S,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylbenzoic acid;
{3-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylphenyl}methanol;
{3-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylphenyl}methanol;
{3-[((2S,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylphenyl}methanol;
{3-[((2R,5S)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylphenyl}methanol;
{3-[((2S,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-4-pyrimidin-2-ylphenyl}methanol;
5-fluoro-2-({6-methyl-1-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-{[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)-5-(trifluoromethyl) pyridine;
2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)-5-(trifluoromethyl)pyridine;
2-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[(1-methyl-4-phenyl-1H-pyrazol-3-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[(1-methyl-4-phenyl-1H-pyrazol-3-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[5-methyl-2-(1,3-oxazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-{[5-methyl-2-(1,3-oxazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({1-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-6-methylpiperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-1-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-6-methylpiperidin-3-yl}methoxy)pyridine;
2-({1-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-6-methylpiperidin-3-yl}methoxy)-5-fluoropyridine;
2-({(3R,6R)-1-[5-chloro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-6-methylpiperidin-3-yl}methoxy)-5-fluoropyridine;
5-fluoro-2-({6-methyl-1-[(4-methylbiphenyl-2-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[(4-methylbiphenyl-2-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-chloro-2-({(6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-chloro-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-4-methyl-2-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-4-methyl-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-methyl-6-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-methyl-6-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-methyl-2-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-methyl-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-{[6-methyl-1-(5-methyl-2-pyridin-2-ylbenzoyl)piperidin-3-yl]methoxy}pyridine;
5-fluoro-2-{[(3R,6R)-6-methyl-1-(5-methyl-2-pyridin-2-ylbenzoyl)piperidin-3-yl]methoxy}pyridine;
5-fluoro-2-{[6-methyl-1-(5-methyl-2-pyridin-3-ylbenzoyl)piperidin-3-yl]methoxy}pyridine;
5-fluoro-2-{[(3R,6R)-6-methyl-1-(5-methyl-2-pyridin-3-ylbenzoyl)piperidin-3-yl]methoxy}pyridine;
5-fluoro-2-({1-[2-(5-fluoropyridin-2-yl)-5-methylbenzoyl]-6-methylpiperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-1-[2-(5-fluoropyridin-2-yl)-5-methylbenzoyl]-6-methylpiperidin-3-yl}methoxy)pyridine;
2-{4-chloro-2-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
2-{4-chloro-2-R(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
2-{4-fluoro-2-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
2-{4-fluoro-2-[(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
5-fluoro-2-({6-methyl-1-[5-methyl-2-(1,3-thiazol-4-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-{[5-methyl-2-(1,3-thiazol-4-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[5-methyl-2-(1H-pyrazol-4-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(1H-pyrazol-4-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(6-methyl-1-[5-methyl-2-(2H-tetrazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-tetrazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[5-methyl-2-(1H-pyrazol-1-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[5-methyl-2-(1H-pyrazol-1-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-{[1-(2-ethoxybenzoyl)-6-methylpiperidin-3-yl]methoxy}-5-fluoropyridine;
2-{[(3R,6R)-1-(2-ethoxybenzoyl)-6-methylpiperidin-3-yl]methoxy}-5-fluoropyridine;
2-{[1-(biphenyl-2-ylcarbonyl)-6-methylpiperidin-3-yl]methoxy}-5-fluoropyridine;
2-{[(3R,6R)-1-(biphenyl-2-ylcarbonyl)-6-methylpiperidin-3-yl]methoxy}-5-fluoropyridine;
5-fluoro-2-({6-methyl-1-[2-(2-phenylethyl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[2-(2-phenylethyl)benzoyl]piperidin-3-yl}methoxy)pyridine;
7-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-1H-indole;
7-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-1H-indole;
2-{2-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
2-{2-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
3-methyl-2-({6-methyl-1-[2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
3-methyl-2-({(3R,6R)-6-methyl-1-[2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-(2-{[2-methyl-5-({[6-(1,3-oxazol-2-yl)pyridin-2-yl]oxy}methyl)piperidin-1-yl]carbonyl}phenyl)pyrimidine;
2-(2-{[(2R,5R)-2-methyl-5-({[6-(1,3-oxazol-2-yl)pyridin-2-yl]oxy}methyl)piperidin-1-yl]carbonyl}phenyl)pyrimidine;
2-{2-[(5-{[(6-isopropylpyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
2-{2-[((2R,5R)-5-{[(6-isopropylpyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
4-{2-[(2-methyl-5-{[(3-methylpyridin-2-yl)oxy]methyl}piperidin-1-yl)carbonyl]phenyl}-1,3-thiazol-2-amine;
4-{2-[((2R,5R)-2-methyl-5-{[(3-methylpyridin-2-yl)oxy]methyl}piperidin-1-yl)carbonyl]phenyl}-1,3-thiazol-2-amine;
5-fluoro-2-({1-[2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl]-6-methylpiperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-1-[2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl]-6-methylpiperidin-3-yl}methoxy)pyridine;
2-{3-fluoro-2-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
2-{3-fluoro-2-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]phenyl}pyrimidine;
5-fluoro-2-({6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[2-(1H-1,2,4-triazol-5-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
3-chloro-2-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
3-chloro-2-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({6-methyl-1-[2-(1H-pyrazol-1-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[2-(1H-pyrazol-1-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-3-phenylpyridine;
2-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-3-phenylpyridine;
5-fluoro-2-({6-methyl-1-[(4-phenylpyridin-3-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
5-fluoro-2-({(3R,6R)-6-methyl-1-[(4-phenylpyridin-3-yl)carbonyl]piperidin-3-yl}methoxy)pyridine;
3-[(5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-2-phenylpyridine;
3-[((2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl)carbonyl]-2-phenylpyridine;
2-chloro-3-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-chloro-3-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-bromo-5-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-bromo-5-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
2-chloro-4-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
and
2-chloro-4-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidin-3-yl}methoxy)pyridine;
or a pharmaceutically acceptable salt thereof.

122 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/568,242Filed 7 Aug 2012 · continuation
Priority: 23 May 2007
Published: US 2012/0295921 A122 Nov 2012
Granted: 29 Oct 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification54 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 1/02
Drugs for disorders of the alimentary tract or the digestive system: stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics

Family

Application60/931,458Us provisional application · filed 23 May 2007
PCT/US2008/006563Parent of this continuation · filed 22 May 2008
US 2012/0295921 A1Pre-grant publication · published 22 Nov 2012
Application12/600,388Parent of this continuation
US 8,242,121 B2Parent of this continuation
US 2010/0168134 A1Published application
US 8,569,311 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of the formula Ic:

wherein:
R1a, R1b and R1c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) —(C═O)m—On—C1-6alkyl, where m is 0 or 1, n is 0 or 1 (wherein if m is 0 or n is 0, a bond is present) and where the alkyl is unsubstituted or substituted with one or more substituents selected from R13,
(4) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R13,
(5) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R13,
(6) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R13,
(7) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R13,
(8) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R13,
(9) —(C═O)m—NR10R11, wherein R10 and R11 are independently selected from the group consisting of:
(a) hydrogen,
(b) C1-6alkyl, which is unsubstituted or substituted with R13,
(c) C3-6alkenyl, which is unsubstituted or substituted with R13,
(d) C3-6alkynyl, which is unsubstituted or substituted with R13,
(e) C3-6cycloalkyl which is unsubstituted or substituted with R13,
(f) phenyl, which is unsubstituted or substituted with R13, and
(g) heterocycle, which is unsubstituted or substituted with R13,
(10) —S(O)2—NR10R11,
(11) —S(O)qR12, where q is 0, 1 or 2 and where R12 is selected from the definitions of R10 and R11,
(12) —CO2H,
(13) —CN, and
(14) —NO2;
R2a, R2b and R2c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) —(C═O)m—On—C1-6alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R13,
(5) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R13,
(6) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R13,
(7) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R13,
(8) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R13,
(9) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R13,
(10) —(C═O)m—NR10R11,
(11) —S(O)2—NR10R11,
(12) —S(O)q—R12,
(13) —CO2H,
(14) —CN, and
(15) —NO2;
R3 is C1-6alkyl or C3-6cycloalkyl, which is unsubstituted or substituted with one or more substituents selected from R13;
R13 is selected from the group consisting of:
(1) halogen,
(2) hydroxyl,
(3) —(C═O)m—On—C1-6alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R14,
(4) —On—(C1-3)perfluoroalkyl,
(5) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R14,
(6) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R14,
(7) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R14,
(8) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R14,
(9) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R14,
(10) —(C═O)m—NR10R11,
(11) —S(O)2—NR10R11,
(12) —S(O)q—R12,
(13) —CO2H,
(14) —CN, and
(15) —NO2;
R14 is selected from the group consisting of:
(1) hydroxyl,
(2) halogen,
(3) C1-6alkyl,
(4) —C3-6cycloalkyl,
(5) —O—C1-6alkyl,
(6) —O(C═O)—C1-6alkyl,
(7) —NH—C1-6alkyl,
(8) phenyl,
(9) heterocycle,
(10) —CO2H, and
(11) —CN;
or a pharmaceutically acceptable salt thereof.

66 more elements

Facts

Application

13/568,242Filed 7 Aug 2012 · continuation

Priority

23 May 2007

Published

US 2012/0295921 A122 Nov 2012

Granted

29 Oct 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification54 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 1/02
Drugs for disorders of the alimentary tract or the digestive system: stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics

Family

Application60/931,458Us provisional application · filed 23 May 2007

PCT/US2008/006563Parent of this continuation · filed 22 May 2008

US 2012/0295921 A1Pre-grant publication · published 22 Nov 2012

Application12/600,388Parent of this continuation

US 8,242,121 B2Parent of this continuation

US 2010/0168134 A1Published application

US 8,569,311 B2This patent

From the US filing history. Foreign family members aren’t listed.