Piperidinyloxy lactone orexin receptor antagonists

1. A compound of the formula I:

wherein:

A is selected from the group consisting of phenyl, naphthyl and heteroaryl;

Q is —O— or —NH—;

X is N or CH;

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

(1) hydrogen,

(2) halogen,

(3) hydroxyl,

(4) —(C═O) m —O n —C 1-6 alkyl, 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 R 4 ,

(5) —(C═O) m —O n —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R 4 ,

(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 4 ,

(7) —(C═O) m —C 2-4 alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R 4 ,

(8) —(C═O) m —O n -phenyl or —(C═O) m —O n -naphthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R 4 ,

(9) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 4 ,

(10) —(C═O) m —NR 10 R 11 , wherein R 10 and R 11 are independently selected from the group consisting of:

(a) hydrogen,

(b) C 1-6 alkyl, which is unsubstituted or substituted with R 4 ,

(c) C 3-6 alkenyl, which is unsubstituted or substituted with R 4 ,

(d) C 3-6 alkynyl, which is unsubstituted or substituted with R 4 ,

(e) C 3-6 cycloalkyl which is unsubstituted or substituted with R 4 ,

(f) phenyl, which is unsubstituted or substituted with R 4 , and

(g) heterocycle, which is unsubstituted or substituted with R 4 ,

(11) —S(O) 2 —NR 10 R 11 ,

(12) —S(O) q —R 12 , where q is 0, 1 or 2 and where R 12 is selected from the definitions of R 10 and R 11 ,

(13) —CO 2 H,

(14) —CN, and

(15) —NO 2 ;

R 3 is selected from C 1-6 alkyl and C 3-6 cycloalkyl, which is unsubstituted or substituted with one or more substituents selected from R 4 ;

R 4 is selected from the group consisting of:

(1) hydroxyl,

(2) halogen,

(3) C 1-6 alkyl,

(4) —C 3-6 cycloalkyl,

(5) —O—C 1-6 alkyl,

(6) —O(C═O)—C 1-6 alkyl,

(7) —NH 2 ,

(8) —NH—C 1-6 alkyl,

(9) —NO 2 ,

(10) phenyl,

(11) heterocycle,

(12) —CO 2 H, and

(13) —CN;

R 5 is hydrogen or C 1-6 alkyl, R 6 is hydrogen or C 1-6 alkyl, and R 7 and R 8 taken together form ═O; or

R 5 and R 6 taken together form ═O, and R 7 is hydrogen or C 1-6 alkyl, and R 8 is hydrogen or C 1-6 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 of the formula Ia:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 of the formula Ib:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein 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 or phenyl,

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

(6) —CN, and

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

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 is methyl.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein Q is —O—.

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein Q is —NH—.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X is N.

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X is CH.

10. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 5 and R 6 taken together form ═O, and R 7 is CH 3 , and R 8 is CH 3 .

11. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 5 is hydrogen, R 6 is hydrogen, and R 7 and R 8 taken together form ═O.

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

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[2-Fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[5-chloro-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-3(1H)-one;

4-(((3R,6R)-1-(2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl)-6-methylpiperidin-3-yl)oxy)-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[3-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[3-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[4-chloro-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[4-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[6-methoxy-2-(2H-1,2,3-triazol-2-yl)pyridin-3-yl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[2-fluoro-6-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[5-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[4-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[2-fluoro-6-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[5-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-1-{[4-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)thiophen-3-yl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-tetrazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(pyrimidin-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-3(1H)-one;

4-({(3R,6R)-1-[(4-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-6-methylpiperidin-3-yl}oxy)-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-({(3R,6R)-1-[(5-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-6-methylpiperidin-3-yl}oxy)-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-(((3R,6R)-6-methyl-1-(2-(pyrimidin-2-yl)thiophene-3-carbonyl)piperidin-3-yl)oxy)furo[3,4-c]pyridin-3(1H)-one;

4-({(3R,6R)-1-[(2-fluoro-6-pyrimidin-2-ylphenyl)carbonyl]-6-methylpiperidin-3-yl}oxy)-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-({(3R,6R)-1-[(3-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-6-methylpiperidin-3-yl}oxy)-1,1-dimethylfuro[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-1(3H)-one;

4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)thiophen-3-yl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-1(3H)-one;

4-{[(3R,6R)-6-methyl-1-{[4-(2H-1,2,3-triazol-2-yl)thiophen-3-yl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-1(3H)-one;

1-[2-({(2R,5R)-2-methyl-5-[(1-oxo-1,3-dihydrofuro[3,4-c]pyridin-4-yl)oxy]piperidin-1-yl}carbonyl)phenyl]cyclopropanecarbonitrile;

4-{[(3R,6R)-1-{[4-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-6-methylpiperidin-3-yl]oxy}furo[3,4-c]pyridin-1(3H)-one;

4-{[(3R,6R)-6-methyl-1-({2-[(methylsulfonyl)methyl]phenyl}carbonyl)piperidin-3-yl]oxy}furo[3,4-c]pyridin-1(3H)-one;

4-{[(3R,6R)-6-methyl-1-{[2-(2H-tetrazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}furo[3,4-c]pyridin-1(3H)-one;

4-({(3R,6R)-6-methyl-1-[(4-pyrimidin-2-ylthiophen-3-yl)carbonyl]piperidin-3-yl}oxy)furo[3,4-c]pyridin-1(3H)-one;

4-({(3R,6R)-6-methyl-1-[(2-pyrimidin-2-ylphenyl)carbonyl]piperidin-3-yl}oxy)furo[3,4-c]pyridin-1(3H)-one;

4-({(3R,6R)-6-methyl-1-[(2-pyrimidin-2-ylthiophen-3-yl)carbonyl]piperidin-3-yl}oxy)furo[3,4-c]pyridin-1(3H)-one;

3,3-dimethyl-7-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]oxy}-2-benzofuran-1(3H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one;

4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-tetrazol-2-yl)phenyl]carbonyl}piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-({(3R,6R)-6-methyl-1-[(2-pyrimidin-2-ylphenyl)carbonyl]piperidin-3-yl}amino)furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)thiophen-3-yl]carbonyl}piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-({(3R,6R)-6-methyl-1-[(2-pyrimidin-2-ylthiophen-3-yl)carbonyl]piperidin-3-yl}amino)furo[3,4-c]pyridin-3(1H)-one;

1,1-dimethyl-4-{methyl[(3R,6R)-6-methyl-1-{[2-(2H-tetrazol-2-yl)phenyl]carbonyl}-piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one;

(1S)-1-methyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one; and

(1R)-1-methyl-4-{[(3R,6R)-6-methyl-1-{[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]amino}furo[3,4-c]pyridin-3(1H)-one;

or a pharmaceutically acceptable salt thereof.

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

14. 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.

15. 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.

16. 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.