Substituted imidazopyridine compounds as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan-2,3-dioxygenase

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

wherein:

each of R 1 and R 2 is independently selected from the group consisting of (1) H and (2) NH 2 ;

one of R 3 and R 6 is H and the other is Y 1 ;

each of R 4 and R 5 is independently selected from the group consisting of (1) H, (2) halogen, (3) C 1-6 alkyl, optionally substituted with one to three halogens, (4) C 3-6 cycloalkyl, (5) C 1-6 alkoxy, optionally substituted with one to three halogens, (6) CN, and (7) —NR g R g′ , each of R g and R g′ is independently selected from the group consisting of H, C 1-6 alkyl, —COH, and —COC 1-6 alkyl;

Y 1 is a group having the following formula:

dashed line “ ” represents an optional double bond;

Q is —C(R a )(R a′ )—, —N(R a )—, or —O—;

T is —C(R a )(R a′ )—, —N(R a )—, or —O—;

R a is selected from the group consisting of (1) H, (2) C 1-10 alkyl, (3) aryl, (4) —C(O)—R e , (5) —SO 2 —NH 2 , and (6) —SO 2 —C 1-4 alkyl; wherein each of the alkyl and aryl is optionally substituted with one to three substituents independently selected from halogen and heterocyclyl;

R a′ is selected from the group consisting of (1) H and (2) C 1-6 alkyl;

R b is C 1-6 alkyl;

each of R c and R d is independently selected from the group consisting of (1) H, (2) C 1-6 alkyl and (3) oxo;

R e is selected from the group consisting of (1) C 1-6 alkyl, (2) aryl and (3) heteroaryl;

m is 0, 1 or 2;

n is 0, 1 or 2; and

p is 0 or 1.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each of R 1 and R 2 is H.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each of R 4 and R 5 is independently selected from the group consisting of (1) H, (2) halogen, (3) C 1-4 alkyl, optionally substituted with one to three halogens.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each of R 4 and R 5 is independently selected from the group consisting of (1) H, (2) halogen, (3) —CF 3 ; and m is 1.

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

R 3 is H;

R 6 is Y 2 having the following formula:

wherein

dashed line “ ” represents an optional double bond;

Q is —CH(R a )— or —N(R a )—;

T is —CH 2 — or —NH—;

R a is selected from the group consisting of (1) H, (2) C 1-6 alkyl, and (3) phenyl; wherein each of the alkyl and phenyl is optionally substituted with one to three substituents independently selected from halogen and a 5- or 6-membered hetero monocyclic group containing one hetero ring atom selected from oxygen, sulfur and nitrogen;

R b is C 1-4 alkyl;

each of R c and R d is independently H or oxo; and

m is 1.

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

R 3 is H;

R 6 is Y 3 having the following formula:

wherein

Q is —N(R a )—;

T is —CH 2 — or —NH—;

R a is selected from the group consisting of (1) H, (2) C 1-6 alkyl, optionally substituted with one to three substituents independently selected from halogen and a 5- or 6-membered hetero monocyclic group containing one oxygen ring atom, and (3) phenyl;

R b is methyl or ethyl; and

n is 0, 1 or 2.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 1 is selected from the group consisting of:

8. The compound of claim 1 having formula (Ia), or a pharmaceutically acceptable salt thereof:

wherein:

R 4 is selected from the group consisting of (1) halogen and (2) C 1-4 alkyl, optionally substituted with one to three halogens;

R 6 is Y 2 having the following formula:

wherein

dashed line “ ” represents an optional double bond;

Q is —CH(R a )— or —N(R a )—;

T is —CH 2 — or —NH—;

R a is selected from the group consisting of (1) H, (2) C 1-4 alkyl, and (3) phenyl; wherein each of the alkyl and phenyl is optionally substituted with one to three substituents independently selected from halogen and heterocyclyl;

R b is C 1-4 alkyl;

each of R c and R d is independently H or oxo;

m is 1; and

n is 0, 1 or 2.

9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 6 is Y 3 having the following formula:

wherein

Q is —N(R a )—;

T is —CH 2 — or —NH—;

R a is selected from the group consisting of (1) H, (2) C 1-4 alkyl, optionally substituted with one to three substituents independently selected from halogen and tetrahydropyranyl, and (3) phenyl; and

R b is methyl.

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

R 5 is selected from the group consisting of (1) halogen and (2) C 1-4 alkyl, optionally substituted with one to three halogens;

R 3 is Y 2 having the following formula:

wherein

dashed line “ ” represents an optional double bond;

Q is —CH(R a )— or —N(R a )—;

T is —CH 2 — or —NH—;

R a is selected from the group consisting of (1) H, (2) C 1-6 alkyl, and (3) phenyl; wherein each of the alkyl and phenyl is optionally substituted with one to three substituents independently selected from halogen and heterocyclyl;

R b is C 1-4 alkyl;

each of R c and R d is independently H or oxo;

m is 1; and

n is 0, 1 or 2.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein R 3 is Y 3 having the following formula:

wherein

Q is —N(R a )—;

T is —CH 2 — or —NH—;

R a is selected from the group consisting of (1) H, (2) C 1-4 alkyl, optionally substituted with one to three substituents independently selected from halogen and tetrahydropyranyl, and (3) phenyl; and

R b is methyl.

12. The compound of claim 1 selected from the group consisting of:

8-(7-(Trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-bromoimidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-chloroimidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(6-(trifluoromethyl)imidazo[1,5-a]pyridin-8-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

6,6-dimethyl-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

3-methyl-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

3-((tetrahydro-2H-pyran-4-yl)methyl)-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-chloroimidazo[1,5-a]pyridin-5-yl)-6,6-dimethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione,

3-phenyl-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

3,6,6-trimethyl-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-chloroimidazo[1,5-a]pyridin-5-yl)-6,6-dimethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione,

6,6-dimethyl-8-(6-(trifluoromethyl)imidazo[1,5-a]pyridin-8-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-2,8-diazaspiro[4.5]decane-1,3-dione,

6,6-dimethyl-3-((tetrahydro-2H-pyran-4-yl)methyl)-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

6,6-dimethyl-3-phenyl-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-bromoimidazo[1,5-a]pyridin-5-yl)-6,6-dimethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-bromoimidazo[1,5-a]pyridin-5-yl)-6,6-dimethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione,

8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-2-oxa-8-azaspiro[4.5]decan-1-one,

2-methyl-8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one,

1-(9-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-3,9-diazaspiro[5.5]undecan-3-yl)ethan-1-one, and

8-(7-(trifluoromethyl)imidazo[1,5-a]pyridin-5-yl)-2,8-diazaspiro[4.5]decan-1-one;

or a pharmaceutically acceptable salt thereof.

13. A composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

14. A method for treating an IDO- and/or TDO-associated disease or disorder in a mammalian subject which comprises administering to the subject an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the disease or disorder is a cancer selected from human glioblastoma and human ovarian adenocarcinoma.