Compounds for the inhibition of indoleamine-2,3-dioxygenase

1. A compound of formula I,

or a pharmaceutically acceptable salt thereof, wherein:

Y is CR;

Y 1 is N;

R 1a is —R, halogen, -haloalkyl, -hydroxyalkyl, —OR, —SR, —CN, —NO 2 , —SO 2 R, —SOR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, or —N(R) 2 ;

R 1b is —R, halogen, -haloalkyl, -hydroxyalkyl, —OR, —SR, —CN, —NO 2 , —SO 2 R, —SOR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, or —N(R) 2 ; or

R 1a and R 1b , together with the atom to which each is attached, may form a fused or spiro ring selected from C 5-10 aryl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, sulfur; each of which is optionally substituted;

Ring A is

each R 2 is independently —R, halogen, -haloalkyl, -hydroxyalkyl, —OR, —SR, —CN, —NO 2 , —SO 2 R, —SOR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, or —N(R) 2 ;

Ring B is C 5-10 aryl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-3 heteroatoms independently selected from X 1 , X 2 , and X 3 , wherein X 1 , X 2 and X 3 are independently selected from nitrogen, oxygen and sulfur, or Ring B is a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from X 1 , X 2 , and X 3 ;

each R 3 is independently —R, halogen, -haloalkyl, -hydroxyalkyl, —OR, —SR, —CN, —NO 2 , —SO 2 R, —SOR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, or —N(R) 2 ;

Ring C is a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from Z, Z 1 , Z 2 , Z 3 , and Z 4 , wherein Z, Z 1 , Z 2 , Z 3 and Z 4 are independently selected from nitrogen, oxygen and sulfur, or Ring C is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from Z, Z 1 , Z 2 , Z 3 , and Z 4 ;

each R is independently hydrogen, C 1-6 aliphatic, C 3-10 aryl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is optionally substituted; or

two R groups on the same atom are taken together with the atom to which they are attached to form a C 3-10 aryl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is optionally substituted;

m is 1 or 2;

n is 0, 1, 2, or 3;

p is 0, 1, 2, or 3; and

r is 0 or 1.

2. The compound of claim 1 , wherein R 1a is —H; or R 1a is halogen, —OR, —NRSO 2 R, or —N(R) 2 .

3. The compound of claim 2 , wherein R 1a is —H; or R 1a is

4. The compound of claim 1 , wherein R 1b is —H; or R 1b is halogen, —OR, —NRSO 2 R, or —N(R) 2 .

5. The compound of claim 4 , wherein R 1b is —H; or R 1b is

6. The compound of claim 1 , wherein each R 2 is independently —H.

7. The compound of claim 1 , wherein each R 2 is independently halogen or —OR.

8. The compound of claim 1 , wherein Ring A is

9. The compound of claim 8 , wherein Ring A is

10. The compound of claim 1 , wherein Ring B is phenyl, cycloheptyl, cyclohexyl, cyclopentyl, cyclobuty, cyclopropyl, or a cyclohexadiene.

11. The compound of claim 1 , wherein Ring B is

12. The compound of claim 1 , wherein Ring C is

13. The compound of claim 1 , of formula II:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , of formula V:

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , selected from the following

16. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable adjuvant, carrier, or vehicle.