Substituted phenyloxetane and phenyltetrahydrofuran compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

wherein:

n is selected from 1, 2 and 3;

p is selected from 0 and 1;

each occurrence of A is independently selected from —CH═ or —N═, provided not all A groups are —N═;

L is selected from —NHC(O)— and —C(O)NH—;

M is selected from —O— and —S—;

W is selected from —C(O)NH— and —NHC(O)—;

R 1 is aryl; wherein the aryl is optionally substituted with 1-3 substituents independently selected from (a) halogen, (b) —CN, (c) C 1-6 alkyl, and (d) —O—C 1-6 alkyl;

R 2 is selected from:

(1) C 1-6 alkyl,

(2) C 3-6 cycloalkyl,

(3) aryl, and

(4) heterocyclyl;

wherein the C 1-6 alkyl of (1) is optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 3-6 cycloalkyl; and

wherein each of the C 3-6 cycloalkyl of (2), aryl of (3), and heterocyclyl of (4) is optionally substituted with 1-3 substituents independently selected from (a) halogen, (b) —CN, and (c) C 1-6 alkyl optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H, (2) halogen, and (3) C 1-6 alkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof,

wherein:

n is selected from 1 and 2;

each occurrence of A is —CH═; and

M is —O—.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

n is selected from 1 and 2;

one occurrence of A is —N═; three occurrences of A are —CH═; and

M is —O—.

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

R 1 is phenyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) —CN.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from:

(1) C 1-6 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 3-6 cycloalkyl,

(2) C 3-6 cycloalkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 1-6 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from:

(1) C 1-4 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) cyclopropyl,

(2) cyclopropyl, optionally substituted with C 1-4 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

n is selected from 1 and 2;

each occurrence of A is —CH═;

L is selected from —NHC(O)— and —C(O)NH—;

M is —O—;

W is selected from —C(O)NH— and —NHC(O)—;

R 1 is phenyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) —CN;

R 2 is selected from:

(1) C 1-6 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 3-6 cycloalkyl,

(2) C 3-6 cycloalkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 1-6 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H and (2) C 1-6 alkyl.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein:

R 2 is selected from:

(1) C 1-4 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) cyclopropyl,

(2) cyclopropyl, optionally substituted with C 1-4 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H and (2) methyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, of formula (La):

wherein:

n is selected from 1 and 2;

p is selected from 0 and 1;

M is —O—;

R 1 is phenyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) —CN;

R 2 is selected from:

(1) C 1-6 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 3-6 cycloalkyl,

(2) C 3-6 cycloalkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 1-6 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H and (2) C 1-6 alkyl.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein:

M is —O—;

R 1 is phenyl, optionally substituted with (a) halogen or (b) —CN;

R 2 is selected from:

(1) C 1-4 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) cyclopropyl,

(2) cyclopropyl, optionally substituted with C 1-4 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H and (2) methyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, of formula (Ib):

wherein:

n is selected from 1 and 2;

p is selected from 0 and 1;

M is —O—;

R 1 is phenyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) —CN;

R 2 is selected from:

(1) C 1-6 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 3-6 cycloalkyl,

(2) C 3-6 cycloalkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 1-6 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H and (2) C 1-6 alkyl.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, of formula (Ic):

wherein:

n is 1 or 2;

p is 1;

M is —O—;

R 1 is phenyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) —CN;

R 2 is selected from:

(1) C 1-6 alkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 3-6 cycloalkyl,

(2) C 3-6 cycloalkyl, optionally substituted with 1-3 substituents independently selected from (a) halogen and (b) C 1-6 alkyl, and

(3) phenyl, optionally substituted with 1-3 halogens; and

R 3 is selected from (1) H and (2) C 1-6 alkyl.

13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein:

n is 1;

R 1 is phenyl, optionally substituted with (a) chloro or (b) —CN;

R 2 is phenyl, optionally substituted with fluoro; and

R 3 is selected from H and methyl.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

N-(4-(3-butyramidooxetan-3-yl)phenyl)-3-chlorobenzamide,

3-(4-(3-chlorobenzamido)phenyl)-N-(4-fluorophenyl)oxetane-3-carboxamide,

3-{4-[(3-chloro-2-fluorobenzene-1-carbonyl)amino]phenyl}-N-(4-fluorophenyl)oxetane-3-carboxamide,

3-{4-[(3-chlorobenzene-1-carbonyl)amino]phenyl}-N-(2-methylcyclopropyl)oxetane-3-carboxamide,

3-{4-[(3-chlorobenzene-1-carbonyl)amino]phenyl}-N-propyloxetane-3-carboxamide,

3-{4-[(3-chlorobenzene-1-carbonyl)amino]phenyl}-N-(3,3,3-trifluoropropyl)oxetane-3-carboxamide,

3-{4-[(3-chlorobenzene-1-carbonyl)amino]phenyl}-N-(cyclopropylmethyl)oxetane-3-carboxamide,

3-{4-[(3-chlorobenzene-1-carbonyl)amino]phenyl}-N-(2-methylcyclopropyl)oxetane-3-carboxamide,

2-(4-(3-chlorobenzamido)phenyl)-N-(3,3,3-trifluoropropyl)tetrahydrofuran-2-carboxamide,

N-(4-(3-butyramidotetrahydrofuran-3-yl)phenyl)-3-chlorobenzamide,

3-(4-(3-chlorobenzamido)phenyl)-N-(4-fluorophenyl)tetrahydrofuran-3-carboxamide,

3-(5-(3-Chlorobenzamido)-6-methylpyridin-2-yl)-N-(4-fluorophenyl)oxetane-3-carboxamide,

3-{5-[(3-chlorobenzene-1-carbonyl)amino]pyridin-2-yl}-N-(4-fluorophenyl)oxetane-3-carboxamide,

3-{5-[(3-chlorobenzene-1-carbonyl)amino]-4-methylpyridin-2-yl}-N-(4-fluorophenyl)oxetane-3-carboxamide,

3-{5-[(3-cyanobenzene-1-carbonyl)amino]-4-methylpyridin-2-yl}-N-(4-fluorophenyl)oxetane-3-carboxamide,

3-{5-[(3-chlorobenzene-1-carbonyl)amino]-3-methylpyridin-2-yl}-N-(4-fluorophenyl)oxetane-3-carboxamide, and

3-{5-[(3-cyanobenzene-1-carbonyl)amino]pyridin-2-yl}-N-(4-fluorophenyl)oxetane-3-carboxamide.

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