Immunomodulator compounds

1. A compound of Formula (II)

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is selected from the group consisting of halogen, C 5-8 cycloalkyl, C 6-10 aryl, wherein the C 6-10 aryl is optionally substituted with 1 to 5 R x substituents;

each R x is independently selected from the group consisting of halogen, —CN, —R c , —CO 2 R a , —CONR a R b , —C(O)R a , —OC(O)NR a R b , —NR b C(O)R a , —NR b C(O) 2 R c , —NR a —C(O)NR a R b , —NR a R b , —OR a , —O—X 1 —OR a , —O—X 1 —CO 2 R a , —O—X 1 —CONR a R b ,

—X 1 —OR a , —X 1 —NR a R b , —X 1 —CO 2 R a , —X 1 —CONR a R b , —SF 5 , and —S(O) 2 NR a R b , wherein each X 1 is a C 1-4 alkylene; each R a and R b is independently selected from hydrogen, C 1-4 alkyl, and C 1-8 haloalkyl; each R c is independently selected from the group consisting of C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl and C 1-8 haloalkyl;

each R 2a , R 2b and R 2c is independently selected from the group consisting of H, halogen, —CN, —R d , —CO 2 R e , —CONR e R f , —C(O)R e , —OC(O)NR e R f , —NR f C(O)R e , —NR f C(O) 2 R d , —NR e —C(O)NR e R f , —NR e R f , —OR e , —O—X 2 —OR e , —O—X 2 —NR e R f , —O—X 2 —CO 2 R e , —O—X 2 —CONR e R f , —X 2 —OR e , —X 2 —NR e R f , —X 2 —CO 2 R e , —X 2 —CONR e R f , —SF 5 , —S(O) 2 NR e R f , and C 6-10 aryl, wherein each X 2 is a C 1-4 alkylene; each R e and R f is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl; each R d is independently selected from the group consisting of C 1-8 alkyl, C 2-8 alkenyl, and C 1-8 haloalkyl;

R 3 is —NR g R h ;

R g is selected from the group consisting of H, C 1-8 haloalkyl and C 1-8 alkyl;

R h is selected from —C 1-8 alkyl, C 1-8 haloalkyl, C 1-8 alkyl-COOH, C 1-8 alkyl-OH, C 1-8 alkyl-CONH 2 , C 1-8 alkyl-SO 2 NH 2 , C 1-8 alkyl-PO 3 H 2 , C 1-8 alkyl-CONOH, C 1-8 alkyl-NR h1 R h2 , —C(O)—C 1-8 alkyl, —C(O)—C 1-8 alkyl-OH, —C(O)—C 1-8 alkyl-COOH, C 3-10 cycloalkyl, —C 3-10 cycloalkyl-COOH, —C 3-10 cycloalkyl-OH, —C 1-8 alkyl-C 3-10 cycloalkyl, C 10 carbocyclyl, —C 1-8 alkyl-C 6-10 aryl, —C 1-8 alkyl-(C═O)—C 6-10 aryl, —C 1-8 alkyl-NH(C═O)—C 1-8 alkenyl, —C 1-8 alkyl-NH(C═O)—C 1-8 alkyl, —C 1-8 alkyl-NH(C═O)—C 1-8 alkynyl, —C 1-8 alkyl-(C═O)—NH—C 1-8 alkyl-COOH, and —C 1-8 alkyl-(C═O)—NH—C 1-8 alkyl-OH optionally substituted with CO 2 H;

wherein

R h1 and R h2 are each independently selected from the group consisting of H, C 1-6 alkyl, and C 1-4 hydroxyalkyl;

the C 1-8 alkyl portions of R h are optionally further substituted with from 1 to 3 substituents independently selected from OH, COOH, SO 2 NH 2 , CONH 2 , CONOH, COO—C 1-8 alkyl, PO 3 H 2 optionally substituted with 1 to 2 C 1-3 alkyl substituents,

the C 10 carbocyclyl, and the C 6-10 aryl portions of R h are optionally substituted with 1 to 3 substituents independently selected from OH, B(OH) 2 , COOH, SO 2 NH 2 , CONH 2 , CONOH, PO 3 H 2 , COO—C 1-8 alkyl, C 1-4 alkyl, C 1-4 alkyl-OH, C 1-4 alkyl-SO 2 NH 2 , C 1-4 alkyl CONH 2 , C 1-4 alkyl-CONOH, C 1-4 alkyl-PO 3 H 2 , C 1-4 alkyl-COOH, and phenyl and

the C 3-10 cycloalkyl portions of R h are optionally substituted with 1 to 4 R w substituents;

each R w substituent is independently selected from C 1-4 alkyl, C 1-4 alkyl-OH, C 1-4 alkyl-COOH, C 1-4 alkyl-SO 2 NH 2 , C 1-4 alkyl CONH 2 , C 1-4 alkyl-CONOH, C 1-4 alkyl-PO 3 H, OH, COO—C 1-8 alkyl, COOH, SO 2 NH 2 , CONH 2 , CONOH, PO 3 H 2 and oxo;

R 4 is selected from the group consisting of pyridinyl and —O—C 1-4 alkyl-pyridinyl wherein the pyridinyl is optionally substituted with 1 to 5 R z ,

each R z is independently selected from the group consisting of halogen, —CN, —R m , —CO 2 R n , —CONR n R p , —C(O)R n , —OC(O)NR n R p , —NR n C(O)R p , —NR n C(O) 2 R m , —NR n —C(O)NR n R p , —NR n R p , —OR n , —O—X 3 —OR n , —O—X 3 —NR n R p , —O—X 3 —CO 2 R n , —O—X 3 —CONR n R p , —X 3 —OR n , —X 3 —NR n R p , —X 3 —CO 2 R n , —X 3 —CONR n R p , —SF 5 , —S(O) 2 R n R p , and —S(O) 2 NR n R p ,

wherein each X 3 is a C 1-4 alkylene; each R n and R p is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl; each R m is independently selected from the group consisting of C 1-8 alkyl, C 2-8 alkenyl, and C 1-8 haloalkyl;

n is 0, 1, 2 or 3;

each R 5 is independently selected from the group consisting of halogen, —CN, —R q , —CO 2 R r , —CONR r R s , —C(O)R r , —OC(O)NR r R s , —NR r C(O)R s , —NR r C(O) 2 R q , —NR r —C(O)NR r R s , —NR r R s , —OR r , —O—X 4 —OR r , —O—X 4 —NR r R s , —O—X 4 —CO 2 R r , —O—X 4 —CONR r R s , —X 4 —OR r , —X 4 —NR r R s , —X 4 —CO 2 R 2 , —X 4 —CONR r R s , —SF 5 , —S(O) 2 NR r R s , wherein each X 4 is a C 1-4 alkylene; each R r and R s is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl; each R q is independently selected from the group consisting of C 1-8 alkyl, and C 1-8 haloalkyl;

R 6a is selected from the group consisting of H, C 1-4 alkyl and C 1-4 haloalkyl;

each R 6b is independently selected from the group consisting of F, C 1-4 alkyl, O—R u , C 1-4 haloalkyl, NR u R v , wherein each R u and R v is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl; and

m is 0, 1, 2, 3 or 4.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof having the formula (IIa)

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof having the formula (IIb)

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein R 1 is phenyl, wherein the phenyl is optionally substituted with 1 to 5 R x substituents.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl optionally substituted with 1 or 2 R x wherein each R x is independently selected from halogen, C 1-8 alkyl, O—C 1-8 alkyl, O—C 1-8 haloalkyl, —NR a R b , and CN.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl optionally substituted with F.

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

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2b and R 2c are both H and R 2a is selected from the group consisting of halogen, C 1-4 alkyl, C 2-4 alkenyl, C 1-3 haloalkyl, —CN, —OMe and OEt.

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2b and R 2c are both H and R 2a is halogen.

10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2b and R 2c are both H and R 2a is Cl.

11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 0, 1 or 2 and each R 5 is independently selected from the group consisting of halogen, —CN, −R q , —NR r R g , and —OR r , wherein each R r and R s is independently selected from hydrogen, C 1-8 alkyl and C 1-8 haloalkyl and each R q is independently selected from the group consisting of C 1-8 alkyl and C 1-8 haloalkyl.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6a is H.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 0.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1 and R 6b is selected from the group consisting of F, C 1-4 alkyl, O—R u , C 1-4 haloalkyl and NR u R v , wherein each R u and R v is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1 and R 6b is F.

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

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein R 4 is selected from the group consisting of pyridinyl, and —O—C 1-2 alkyl-pyridinyl, wherein the pyridinyl is optionally substituted with 1 to 2 R z , wherein each R z is independently selected from the group consisting of halogen, —CN, —CO 2 R n , —R n R p , —OR n , and piperidinyl optionally substituted with OH.

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from the group consisting of:

20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is NR g R h , wherein R g is selected from the group consisting of H, C 1-8 haloalkyl and C 1-8 alkyl, and wherein R h is —C 1-8 alkyl substituted with from 1 to 3 substituents independently selected from OH, COOH, SO 2 NH 2 , CONH 2 , CONOH, COO—C 1-8 alkyl, and PO 3 H 2 .

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is NHR h , wherein R h is —C 1-8 alkyl substituted with from 1 to 2 substituents independently selected from OH, COOH, CONH 2 , PO 3 H 2 .

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein R 3 is selected from the group consisting of:

24. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

25. The compound of claim 1 , selected from the group consisting of

26. The compound of claim 1 , selected from the group consisting of

27. The compound of claim 1 , having the formula

28. The compound of claim 1 , having the formula

29. The compound of claim 1 , having the formula

30. The compound of claim 1 , having the formula