2,5-disubstituted piperidine orexin receptor antagonists

1. A compound of the formula IIa:

wherein:

B is selected from the group consisting of phenyl, napthyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinolinyl, and isoquinolinyl;

R 1a , R 1b and R 1c are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) hydroxyl,

(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl, phenyl or napthyl,

(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,

(6) heteroaryl, wherein heteroaryl is selected from triazolyl, oxazolyl, pyrrolyl, imidazolyl, indolyl, pyridyl, and pyrimidinyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,

(7) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,

(8) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 , and

(9) —NH—C 1-6 alkyl, or —N(C 1-6 alkyl)(C 1-6 alkyl), which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ;

R 2a , R 2b and R 2c may be absent if the valency of B does not permit such substitution and are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) hydroxyl,

(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl or napthyl,

(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,

(6) heteroaryl, wherein heteroaryl is selected from pyrrolyl, imidazolyl, indolyl, pyridyl, and pyrimidinyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,

(7) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ,

(8) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 , and

(9) —NH—C 1-6 alkyl, or —N(C 1-6 alkyl)(C 1-6 alkyl), which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ;

R 3 is C 1-6 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein R 1a , R 1b and R 1c are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) C 1-6 alkyl,

(4) triazolyl,

(5) oxazolyl,

(6) pyrimidinyl, and

(7) phenyl.

3. The compound of claim 1 wherein R 1c is hydrogen and R 1a and R 1b are independently selected from the group consisting of:

(1) hydrogen,

(2) chloro,

(3) fluroro,

(4) methyl,

(5) triazolyl,

(6) oxazolyl,

(7) pyrimidinyl, and

(8) phenyl.

4. The compound of claim 1 wherein R 2a , R 2b and R 2c are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) C 1-6 alkyl, which is unsubstituted or substituted with halogen,

(4) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, and

(5) —NH—C 1-6 alkyl, or —N(C 1-6 alkyl)(C 1-6 alkyl), which is unsubstituted or substituted with halogen.

5. The compound of claim 1 wherein R 2c is hydrogen, and R 2a and R 2b are independently selected from the group consisting of:

(1) hydrogen,

(2) chloro,

(3) fluoro,

(4) bromo,

(5) methoxy,

(6) t-butoxy,

(7) difluoromethyl, and

(8) trifluoromethyl.

6. The compound of claim 1 wherein R 3 is methyl.

7. A compound which is selected from the group consisting of:

5-[(3-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5R)-5-[(3-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5S)-5-[(3-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5S)-5-[(3-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5R)-5-[(3-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

5-[(2-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5R)-5-[(2-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5S)-5-[(2-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5S)-5-[(2-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5R)-5-[(2-fluorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

5-[(3-chlorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5R)-5-[(3-chlorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5S)-5-[(3-chlorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5S)-5-[(3-chlorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5R)-5-[(3-chlorophenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

5-[(4-methoxyphenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5R)-5-[(4-methoxyphenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5S)-5-[(4-methoxyphenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2R,5S)-5-[(4-methoxyphenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

(2S,5R)-5-[(4-methoxyphenoxy)methyl]-2-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine;

7-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

7-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

7-({(3S,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

7-({(3R,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

7-({(3S,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

7-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)-isoquinoline;

7-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)-isoquinoline;

7-({(3S,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)-isoquinoline;

7-({(3R,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)-isoquinoline;

7-({(3S,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)-isoquinoline;

1-({6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)isoquinoline;

1-({(3R,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)isoquinoline;

1-({(3S,6S)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)isoquinoline;

1-({(3R,6S)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)isoquinoline;

1-({(3S,6R)-6-methyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)isoquinoline;

2-({6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

2-({(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

2-({(3S,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

2-({(3R,6S)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

and

2-({(3S,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)benzoyl]piperidine-3-yl}methoxy)quinoline;

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

9. A method for enhancing the quality of sleep in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

10. A method for treating insomnia in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

11. A method for treating or controlling obesity in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.