Therapeutic compounds and methods of use thereof

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof; wherein

each R AA is independently selected from the group consisting of F, Cl, Br, I, —CN, —C(═O)OR A1 , —SO 2 R A1 , —OR A1 , —(X RA )-(3-15 membered carbocyclyl), —(X RA )-(6-12 membered aryl), —(X RA )-(5-12 membered heteroaryl), and —R A2 , wherein said 3-15 membered carbocyclyl, 6-12 membered aryl, and 5-12 membered heteroaryl of R AA is optionally substituted with from 1 to 5 substituents R b that are independently selected from the group consisting of F, Cl, Br, I, C 1-4 alkyl, C 1-4 haloalkyl, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, and C 1-4 (halo)alkoxy; R A1 is selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 1-8 haloalkyl, C 3-8 cycloalkyl, phenyl and benzyl; R A2 is selected from the group consisting of C 1-8 alkyl that is optionally substituted with one or more substituents selected from oxo, fluoro, hydroxy, amino, C 1-4 alkylamino and di(C 1-4 alkyl)amino; X RA is selected from the group consisting of absent, —C(═O)—, and C 1-4 alkylene; wherein any C 1-4 alkylene, of X RA is optionally substituted with 1 to 3 substituents selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, and phenyl that is optionally substituted with 1 to 5 substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino;

ring “A” is a 5-6 membered heterocycle;

R 1a is H or C 1-4 alkyl;

R 1b is H or C 1-4 alkyl;

R 2 is selected from the group consisting of H, F, Cl, Br, I, —CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 haloalkyl and C 1-8 alkoxy;

R 3 , R 4 , and R 5 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 haloalkyl and C 1-8 alkoxy;

R 6 is selected from the group consisting of H, C 1-8 alkyl, C 3-8 cycloalkyl, aryl, and aryl(C 1-4 alkyl); and R 7 is selected from the group consisting of 3-15 membered heterocyclyl, 5-12 membered heteroaryl, —C(O)N(R c ) 2 and —C(═NCN)N(R c ) 2 ; or R 6 and R 7 , together with the nitrogen to which they are attached, form a 3-15 membered heterocyclyl or 5-12 membered heteroaryl: wherein any C 1-8 alkyl, C 3-8 cycloalkyl, aryl, aryl(C 1-4 alkyl), 3-15 membered heterocyclyl, and 5-12 membered heteroaryl is optionally substituted with one or more groups R d that are independently selected from the group consisting of F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino;

each R c is independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, phenyl and benzyl; and

n is 0, 1, 2, 3, 4, 5, or 6;

provided at least one of R 2 , R 3 , R 4 , and R 5 is not H.

2. A compound of formula (Ix):

or a pharmaceutically acceptable salt thereof; wherein,

each R AA is independently selected from the group consisting of F, Cl, Br, I, —CN, —C(═O)OR A1 , —SO 2 R A1 , —OR A1 , —(X RA )-(3-15 membered carbocyclyl), —(X RA )-(6-12 membered aryl), —(X RA )-(5-12 membered heteroaryl), and —R A2 , wherein said 3-15 membered carbocyclyl, 6-12 membered aryl, and 5-12 membered heteroaryl of R AA is optionally substituted with from 1 to 5 substituents R b that are independently selected from the group consisting of F, Cl, Br, I, C 1-4 alkyl, C 1-4 haloalkyl, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 (halo)alkoxy, and —C(O)N(R c ) 2 ; R A1 is selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 1-8 haloalkyl, C 3-8 cycloalkyl, phenyl and benzyl; R A2 is selected from the group consisting of C 1-8 alkyl that is optionally substituted with one or more substituents selected from oxo, fluoro, hydroxy, amino, C 1-4 alkylamino and di(C 1-4 alkyl)amino; X RA is selected from the group consisting of absent, —C(═O)—, and C 1-4 alkylene; wherein any C 1-4 alkylene, of X RA is optionally substituted with 1 to 3 substituents selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, and phenyl that is optionally substituted with 1 to 5 substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino;

ring “A” is a 5-12 membered heteroaryl, or a 3-15 membered heterocyclyl;

Ring B is a 5, 6, or 7 membered carbocyclyl or a 5, 6, or 7 membered heterocyclyl, which 5, 6, or 7 membered carbocyclyl and 5, 6, or 7 membered heterocyclyl is optionally substituted with one or more groups independently selected from C 1-4 alkyl, halo, and haloC 1-4 alkyl;

R 1b is H or C 1-4 alkyl;

R 3 , R 4 , and R 5 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 haloalkyl and C 1-8 alkoxy;

R 6 is selected from the group consisting of H, C 1-8 alkyl, C 3-8 cycloalkyl, aryl, and aryl(C 1-4 alkyl); and R 7 is selected from the group consisting of C 1-8 alkyl, 3-15 membered heterocyclyl, 5-12 membered heteroaryl, —C(O)N(R c ) 2 and —C(═NCN)N(R c ) 2 ; or R 6 and R 7 , together with the nitrogen to which they are attached, form a 3-15 membered heterocyclyl or 5-12 membered heteroaryl; wherein any C 1-8 alkyl, C 3-8 cycloalkyl, aryl, aralkyl, 3-15 membered heterocyclyl, and 5-12 membered heteroaryl is optionally substituted with one or more groups R d that are independently selected from the group consisting of F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino; each R c is independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, phenyl and benzyl; and

n is 0, 1, 2, 3, 4, 5, or 6.

3. The compound of formula (Ix) of claim 2 :

or a pharmaceutically acceptable salt thereof; wherein,

each R AA is independently selected from the group consisting of F, Cl, Br, I, —CN, —OR A1 , —(X RA )-(3-15 membered carbocyclyl), —(X RA )-(6-12 membered aryl), —(X RA )-(5-12 membered heteroaryl), and —R A2 , wherein said (3-15 membered carbocyclyl), 6-12 membered aryl, and 5-12 membered heteroaryl of R AA is optionally substituted with from 1 to 5 substituents R b that are independently selected from the group consisting of F, Cl, Br, I, C 1-4 alkyl, C 1-4 haloalkyl, amino, C 1-4 alkylamino and di(C 1-4 alkyl)amino, and C 1-4 (halo)alkoxy; R A1 is selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 1-8 haloalkyl, C 3-8 cycloalkyl, phenyl and benzyl;

R A2 is selected from the group consisting of C 1-8 alkyl that is optionally substituted with one or more substituents selected from oxo, fluoro, hydroxy, amino, C 1-4 alkylamino and di(C 1-4 alkyl)amino; X RA is selected from the group consisting of absent, —C(═O)—, and C 1-4 alkylene; wherein any C 1-4 alkylene, of X RA is optionally substituted with 1 to 3 substituents selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, and phenyl that is optionally substituted with 1 to 5 substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-8 alkylamino and C 1-4 dialkylamino;

ring “A” is a 5-12 membered heteroaryl, or a 3-15 membered heterocyclyl;

Ring B is a 5, 6, or 7 membered carbocyclyl or a 5, 6, or 7 membered heterocyclyl, which 5, 6, or 7 membered carbocyclyl and 5, 6, or 7 membered heterocyclyl is optionally substituted with one or more groups independently selected from C 1-4 alkyl, halo, and haloC 1-4 alkyl;

R 1b is H or C 1-4 alkyl;

R 3 , R 4 , and R 5 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 haloalkyl and C 1-8 alkoxy;

R 6 is selected from the group consisting of H, C 1-8 alkyl, C 3-8 cycloalkyl, aryl, and aryl(C 1-4 alkyl); and R 7 is selected from the group consisting of C 1-8 alkyl, 3-15 membered heterocyclyl, 5-12 membered heteroaryl, —C(O)N(R c ) 2 and —C(═NCN)N(R c ) 2 ; or R 6 and R 7 , together with the nitrogen to which they are attached, form a 3-15 membered heterocyclyl or 5-12 membered heteroaryl; wherein any C 1-8 alkyl, C 3-8 cycloalkyl, aryl, aralkyl, 3-15 membered heterocyclyl, and 5-12 membered heteroaryl is optionally substituted with one of more groups R d that are independently selected from the group consisting of F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino;

each R c is independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, phenyl and benzyl; and

n is 0, 1, 2, 3, 4, 5, or 6.

4. The compound of claim 2 which is a compound of formula Ic:

wherein the ring B is a 5, 6, or 7 membered carbocyclyl or a 5, 6, or 7 membered heterocyclyl; or a pharmaceutically acceptable salt thereof.

5. The compound of claim 2 which is a compound of formula Id:

wherein X is O, S, SO, or SO 2 ; m is 0, 1, 2, 3, 4 or 5; and p is 0, 1, 2, 3, 4, or 5: or a pharmaceutically acceptable salt thereof.

6. The compound of claim 2 , which is a compound of formula Ih:

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 2 , which is a compound of formula Ij:

wherein m is 0, 1, 2, 3, 4 or 5; and p is 0, 1, 2, 3, 4, or 5; or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein the group

is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , wherein the group

is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 , wherein the group

is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 2 which is a compound of formula Ik:

or a pharmaceutically acceptable salt thereof; wherein,

each R AA is independently selected from the group consisting of F, Cl, Br, I, —CN, —OR A1 , —(X RA )-(3-15 membered carbocyclyl), —(X RA )-(6-12 membered aryl), —(X RA )-(5-12 membered heteroaryl), and —R A2 , wherein said (3-15 membered carbocyclyl), 6-12 membered aryl, and 5-12 membered heteroaryl of R AA is optionally substituted with from 1 to 5 substituents R b that are independently selected from the group consisting of F, Cl, Br, I, C 1-4 alkyl, C 1-4 haloalkyl, amino, C 1-4 alkylamino and di(C 1-4 alkyl)amino, and C 1-4 (halo)alkoxy; R A1 is selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 1-8 haloalkyl, C 3-8 cycloalkyl, phenyl and benzyl;

R A2 is selected from the group consisting of C 1-8 alkyl that is optionally substituted with one or more substituents selected from oxo, fluoro, hydroxy, amino, C 1-4 alkylamino and di(C 1-4 alkyl)amino; X RA is selected from the group consisting of absent, —C(═O)—, and C 1-4 alkylene; wherein any C 1-4 alkylene, of X RA is optionally substituted with 1 to 3 substituents selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, and phenyl that is optionally substituted with 1 to 5 substituents selected from, F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino;

ring “A” is a 5-12 membered heteroaryl, or a 3-15 membered heterocyclyl;

Ring B is a 5, 6, or 7 membered carbocyclyl or a 5, 6, or 7 membered heterocyclyl, which 5, 6, or 7 membered carbocyclyl and 5, 6, or 7 membered heterocyclyl is optionally substituted with one or more groups independently selected from C 1-4 alkyl, halo, and haloC 1-4 alkyl;

R 1b is H or C 1-4 alkyl;

R 3 , R 4 , and R 5 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 haloalkyl and C 1-8 alkoxy;

R 6 is selected from the group consisting of H, C 1-8 alkyl, C 3-8 cycloalkyl, aryl, and aryl(C 1-4 alkyl); and R 7 is selected from the group consisting of C 1-8 alkyl, 3-15 membered heterocyclyl, 5-12 membered heteroaryl, —C(O)N(R c ) 2 and —C(═NCN)N(R c ) 2 ; or R 6 and R 7 , together with the nitrogen to which they are attached, form a 3-15 membered heterocyclyl or 5-12 membered heteroaryl; wherein any C 1-8 alkyl, C 3-8 cycloalkyl, aryl, aralkyl, 3-15 membered heterocyclyl, and 5-12 membered heteroaryl is optionally substituted with one of more groups R d that are independently selected from the group consisting of F, Cl, Br, I, —NH 2 , —OH, —CN, —NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 (halo)alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino;

each R c is independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, phenyl and benzyl;

n is 0, 1, 2, 3, 4, 5, or 6; and

X is CH 2 , NR A2 , S, or O.

12. The compound of claim 2 which is a compound of formula Im:

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 2 which is a compound of formula Io:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 2 , which is a compound of formula Is:

wherein m is 0, 1, 2, 3, 4 or 5; and p is 0, 1, 2, 3, 4, or 5; or a pharmaceutically acceptable salt thereof.

15. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 2 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 2 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

19. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

20. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 2 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

22. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

23. A compound of selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

24. The compound of claim 2 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

25. A compound having formula:

or a pharmaceutically acceptable salt thereof.

26. A pharmaceutical composition comprising a compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.