Substituted diazepan orexin receptor antagonists

1. A compound of the formula Ib or Ic:

wherein:

R 1 is selected from the group consisting of:

(1) phenyl, where the phenyl is substituted with R 1a , R 1b and R 1c , and

(2) napthyl, where the napthyl is substituted with R 1a , R 1b and R 1c ;

(3) heteroaryl, where the heteroaryl is substituted with R 1a , R 1b and R 1c ;

R 2 is heteroaryl, where the heteroaryl is substituted with R 2a , R 2b and R 2c ;

R 1a , R 1b , R 1c , R 2a , R 2b and R 2c 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 13 ,

(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 13 ,

(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(7) —(C═O) m —C 2-4 alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(8) —(C═O) m —O n -phenyl or —(C═O) m —O n -napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(9) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 13 ,

(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 one or more substituents selected from R 13 ,

(c) C 3-6 alkenyl, which is unsubstituted or substituted with one or more substituents selected from R 13 ,

(d) cycloalkyl, which is unsubstituted or substituted with one or more substituents selected from R 13 ,

(e) phenyl, which is unsubstituted or substituted with one or more substituents selected from R 13 , and

(f) heterocycle, which is unsubstituted or substituted with one or more substituents selected from R 13 ,

(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,

(15) —NO 2 , and

(16) —B(OH) 2 ;

R 7 , R 9 , and R 11 are independently selected from the group consisting of:

(1) hydrogen,

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(3) —O—C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 , and

(4)-phenyl, where the phenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

with the proviso that at least two of R 7 , R 9 , or R 11 are other than hydrogen;

R 13 is selected from the group consisting of:

(1) halogen,

(2) hydroxyl,

(3) —(C═O) m —O n —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 14 ,

(4) —O n —(C 1-3 )perfluoroalkyl,

(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 14 ,

(6) —(C═O) m —C 2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R 14 ,

(7) —(C═O) m —O n -phenyl or —(C═O) m —O n -napthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R 14 ,

(8) —(C═O) m —O n -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 14 ,

(9) —(C═O) m —NR 10 R 11 ,

(10) —S(O) 2 —NR 10 R 11 ,

(11) —S(O) q —R 12 ,

(12) —CO 2 H,

(13) —CN, and

(14) —NO 2 ;

R 14 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—C 1-6 alkyl,

(8) phenyl,

(9) heterocycle,

(10) —CO 2 H, and

(11) —CN;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein R 1 is phenyl, which is unsubstituted or substituted with one or more of:

(1) halogen,

(2) hydroxyl,

(3) —O n —C 1-6 alkyl, where n is 0 or 1 (wherein if n is 0, a bond is present) and where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(4) —O n -phenyl, where the phenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(5)-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 13 ,

(6) —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 one or more substituents selected from R 13 ,

(7) —S(O) 2 —NR 10 R 11 ,

(8) —CO 2 H,

(9) —CN,

(10) —NO 2 , and

(11) —B(OH) 2 .

3. The compound of claim 1 wherein R 1 is selected from the group consisting of:

(1) phenyl,

(2) biphenyl,

(3) 2,6-dimethoxyphenyl,

(4) 2,4-dichlorophenyl,

(5) 2,6-dichlorophenyl,

(6) 2,3-difluorophenyl,

(7) 2,4-difluorophenyl,

(8) 2,6-difluorophenyl,

(9) 2-methoxy-4-methyl-phenyl,

(10) 3-methoxy-biphenyl,

(11) 3-methyl-biphenyl,

(12) 5-methyl-2-thiazolyl-phenyl, and

(13) 5-methyl-2-triazolyl-phenyl.

4. The compound of claim 1 wherein R 2 is heteroaryl, which is unsubstituted or substituted with one or more of:

(1) halogen,

(2) hydroxyl,

(3) —O n —C 1-6 alkyl, where n is 0 or 1 (wherein if n is 0, a bond is present) and where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(4) —O n -phenyl, where the phenyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

(5) -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R 13 ,

(6) —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 one or more substituents selected from R 13 ,

(7) —S(O) 2 —NR 10 R 11 ,

(8) —CO 2 H,

(9) —CN, and

(10) —NO 2 .

5. The compound of claim 4 wherein R 2 is selected from the group consisting of:

(1) benzimidazolyl,

(2) benzothiazolyl,

(3) benzoxazolyl,

(4) quinazolinyl,

(5) quinolinyl,

(6) thiadiazolyl,

(7) thiazolyl, and

(8) oxazolopyridyl,

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

6. The compound of claim 5 wherein R 2 is selected from the group consisting of:

(1) benzimidazol-2-yl,

(2) 1,3-benzothiazol-2-yl,

(3) 1,3-benzoxazol-2-yl,

(4) 2-quinazolinyl,

(5) 1-quinolin-2-yl,

(6) 1,2,4-thiadiazol-5-yl,

(7) 1,3-thiazol-2-yl, and

(8) oxazolo[5,4-b]pyridyl,

which is unsubstituted or substituted with methyl, fluoro, chloro or phenyl.

7. The compound of claim 1 wherein R 7 , R 9 , and R 11 are independently selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R 13 ,

with the proviso that at least two of R 7 , R 9 , or R 11 are other than hydrogen.

8. The compound of claim 1 wherein:

of the formula 1b wherein R 7 is —C 1-6 alkyl and R 9 is —C 1-6 alkyl; or

of the formula 1c wherein R 9 is —C 1-6 alkyl and R 11 is C 1-6 alkyl.

9. A compound which is selected from the group consisting

2-{6,7-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline;

2-{5,6-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline;

2-{6,7-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline;

2-{5,6-dimethyl-4-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline;

2-{6,7-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-1,3-benzoxazole;

2-{5,6-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline;

6-fluoro-2-{4-[2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl]-5,6-dimethyl-1,4-diazepan-1-yl}quinazoline;

6-fluoro-2-{-4-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl]-5,6-dimethyl-1,4-diazepan-1-yl}quinazoline;

6-fluoro-2-[4-(2-iodobenzoyl)-5,6-dimethyl-1,4-diazepan-1-yl]quinazoline;

2-{5,6-dimethyl-4-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-5-fluoro-1,3-benzoxazole;

5-bromo-2-{5,6-dimethyl-4-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-1,3-benzoxazole;

2-{5,6-dimethyl-4-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-4-methyl-1,3-benzoxazole;

7-chloro-2-{5,6-dimethyl-4-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-1,3-benzoxazole;

7-chloro-2-{5,6-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-1,3-benzoxazole;

2-(4-benzoyl-5,6-dimethyl-1,4-diazepan-1-yl)-6-fluoroquinazoline;

2-{5,6-dimethyl-4-[5-methyl-2-(1,3-oxazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-4-methyl-1,3-benzoxazole;

5,6-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1-(4-phenyl-1,3-thiazol-2-yl)-1,4-diazepane;

5,6-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1-(5-phenyl-1,3-thiazol-2-yl)-1,4-diazepane;

5,6-dimethyl-4-[5-methyl-2-(1,3-oxazol-2-yl)benzoyl]-1-(5-phenyl-1,3-thiazol-2-yl)-1,4-diazepane; and

2-{5,6-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-7-methyl[1,3]oxazolo[5,4-b]pyridine;

or a pharmaceutically acceptable salt thereof.

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