Therapeutic compounds and uses thereof

1. A compound of formula (I):

or a salt thereof, wherein:

R 1 is selected from the group consisting of, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, and C 1-6 alkoxy;

X is N(R a ), or S;

each R a is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, and C 3 -C 10 carbocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, and C 3 -C 10 carbocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, C 1-6 alkoxy, and C 1 -C 6 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo;

R 3 and R 4 are each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups R b ; or R 3 and R 4 taken together with the atoms to which they are attached form a C 3 -C 10 carbocyclyl or 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, which C 3 -C 10 carbocyclyl and 3-12 membered heterocyclyl is optionally substituted with one or more groups R b ;

R 5 is hydrogen or C 1-6 alkyl, or R 4 and R 5 taken together with the atoms to which they are attached form a C 3 -C 10 carbocyclyl or 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, which C 3 -C 10 carbocyclyl and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, oxo, halo, hydroxy, and —NO 2 , wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, and C 3-6 carbocyclyl, is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, and C 1-6 alkoxy;

each R b is independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, oxo, halo, —NO 2 , —N(R c ) 2 , —CN, —C(O)—N(R c ) 2 , —S(O)—N(R c ) 2 , —S(O) 2 —N(R c ) 2 , —O—R c , —S—R c , —O—C(O)—R c , —C(O)—R c , —C(O)—OR c , —S(O)—R c , —S(O) 2 —R c , —C(O)—N(R c ) 2 , —N(R c )—C(O)—R c , —N(R c )—S(O)—R c , and —N(R c )—S(O) 2 —R c , wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, —NO 2 , —N(R c ) 2 , —CN, —C(O)—N(R c ) 2 , —S(O)—N(R c ) 2 , —S(O) 2 —N(R c ) 2 , —O—R c , —S—R c , —O—C(O)—R c , —C(O)—R c , —C(O)—O—R c , —S(O)—R c , —S(O) 2 —R c , —C(O)—N(R c ) 2 , —N(R c )—C(O)—R c , —N(R c )—S(O)—R c , and —N(R c )—S(O) 2 —R c ;

each R c is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and C 1 -C 6 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo; or two R c are taken together with the nitrogen to which they are attached to form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo and C 1-3 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo;

ring A is a 5- or 6-membered heterocyclyl or a 5- or 6-membered carbocyclyl, which 5- or 6-membered heterocyclyl and 5- or 6-membered carbocyclyl is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, halo, —NO 2 , —N(R d ) 2 , —CN, —C(O)—N(R d ) 2 , —S(O)—N(R d ) 2 , —S(O) 2 —N(R d ) 2 , —O—R d , —S—R d , —O—C(O)—R d , —C(O)—R d , —C(O)—O—R d , —S(O)—R d , —S(O) 2 —R d , —C(O)—N(R d ) 2 , —N(R d )—C(O)—R d , —N(R d )—S(O)—R d , —O—C(O)—N(R d ) 2 , —N(R d )—C(O)—O—R d , —N(R d )—C(O)—N(R d ) 2 , and —N(R d )—S(O) 2 —R d , wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo halo, —NO 2 , —N(R d ) 2 , —CN, —C(O)—N(R d ) 2 , —S(O)—N(R d ) 2 , —S(O) 2 —N(R d ) 2 , —O—R d , —S—R d , —O—C(O)—R d , —C(O)—R d , —C(O)—O—R d , —S(O)—R d , —S(O) 2 —R d , —C(O)—N(R d ) 2 , —N(R d )—C(O)—R d , —N(R d )—S(O)—R d , —O—C(O)—N(R d ) 2 , —N(R d )—C(O)—O—R d , —N(R d )—C(O)—N(R d ) 2 , and —N(R d )—S(O) 2 —R d ;

each R d is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups R f ; or two R d are taken together with the nitrogen to which they are attached to form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups R f ;

each R e is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and C 1 -C 6 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo; or two R e are taken together with the nitrogen to which they are attached to form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo and C 1-3 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo; or one R e taken together with R 3 and the atoms to which they are attached form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, C 1-6 alkoxy and C 3 -C 10 carbocyclyl; or one R e taken together with R 4 and the atoms to which they are attached form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxy, C 1-6 alkoxy and C 3 -C 10 carbocyclyl;

each R f is independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, oxo, halo, —NO 2 , —N(R g ) 2 , —CN, —C(O)—N(R g ) 2 , —S(O)—N(R g ) 2 , —S(O) 2 —N(R g ) 2 , —O—R g , —S—R g , —O—C(O)—R g , —C(O)—R g , —C(O)—OR g , —S(O)—R g , —S(O) 2 —R g , —N(R g )—C(O)—R g , —N(R g )—S(O)—R g , —N(R g )—C(O)—N(R g ) 2 , and —N(R g )—S(O) 2 —R g , wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, —NO 2 , —N(R g ) 2 , —CN, —C(O)—N(R g ) 2 , —S(O)—N(R g ) 2 , —S(O) 2 —N(R g ) 2 , —O—R g , —S—R g , —O—C(O)—R g , —C(O)—R g , —C(O)—O—R g , —S(O)—R g , —S(O) 2 —R g , —N(R g )—C(O)—R g , —N(R g )—S(O)—R g , —N(R g )—C(O)—N(R g ) 2 , and —N(R g )—S(O) 2 —R g ; and

each R g is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, C 1-6 alkoxy, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and C 1 -C 6 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo; or two R g are taken together with the nitrogen to which they are attached to form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo and C 1-3 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo.

2. The compound of claim 1 which has a formula selected from formulae I(a-j):

wherein ring A is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, halo, —NO 2 , —N(R d ) 2 , —CN, —C(O)—N(R d ) 2 , —S(O)—N(R d ) 2 , —S(O) 2 —N(R d ) 2 , —O—R d , —S—R d , —O—C(O)—R d , —C(O)—R d , —C(O)—O—R d , —S(O)—R d , —S(O) 2 —R d , —C(O)—N(R d ) 2 , —N(R d )—C(O)—R d , —N(R d )—S(O)—R d , and —N(R d )—S(O) 2 —R d , wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, —NO 2 , —N(R d ) 2 , —CN, —C(O)—N(R d ) 2 , —S(O)—N(R d ) 2 , —S(O) 2 —N(R d ) 2 , —O—R d , —S—R d , —O—C(O)—R d , —C(O)—R d , —C(O)—O—R d , —S(O)—R d , —S(O) 2 —R d , —C(O)—N(R d ) 2 , —N(R d )—C(O)—R d , —N(R d )—S(O)—R d , —N(R d )—S(O) 2 —R d ; and salts thereof.

3. The compound of claim wherein ring A is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, phenyl, halo, and —O—R d , wherein any C 1-6 alkyl and phenyl is optionally substituted with one or more groups independently selected from halo.

4. The compound of claim 1 wherein ring A is optionally substituted with one or more groups independently selected from the group consisting of methoxy, 4-chlorophenyl, fluoro, and methyl.

5. The compound of claim 1 wherein R 1 is C 1-6 alkyl, optionally substituted with one or more groups independently selected from the group consisting of oxo, halo, amino, hydroxy, and C 1-6 alkoxy.

6. The compound of claim 1 wherein R 1 is methyl or ethyl.

7. The compound of claim 1 wherein X is S.

8. The compound of claim 1 wherein X is N(H).

9. The compound of claim 1 wherein R 3 is hydrogen or C 1-6 alkyl.

10. The compound of claim 1 wherein R 3 is hydrogen, methyl, or ethyl.

11. The compound of claim 1 wherein R 4 is hydrogen, C 1-6 alkyl, C 3 -C 10 carbocyclyl, or 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein each C 1-6 alkyl, C 3 -C 10 carbocyclyl, and 3-12 membered heterocyclyl is optionally substituted with one or more groups R b .

12. The compound of claim 1 wherein R 4 is selected from the group consisting of H, phenyl, methyl, ethyl, cyclohexyl, 4-fluorophenyl, 4-methoxyphenyl, 4-chlorophenyl, 1-methyltriazol-4-yl, 1-phenylpyrazol-4-yl, 1-methylpyrazol-4-yl, pyrid-3-yl, 4-(phenyl sulfonyl)phenyl, 4-hydroxyphenyl, 4-(methoxycarbonyl)phenyl, 2-chlorophenyl, 2-fluorophenyl, 4-carboxyphenyl,

13. The compound of claim 1 wherein R 3 and R 4 taken together with the atoms to which they are attached form a C 3 -C 10 carbocyclyl or 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, which C 3 -C 10 carbocyclyl and 3-12 membered heterocyclyl is optionally substituted with one or more groups R b .

14. The compound of claim 1 wherein R 3 and R 4 taken together with the atoms to which they are attached form a C 3 -C 10 carbocyclyl or 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur selected from the group consisting of: cyclohexane, cyclopentane, piperidine, and indane, which C 3 -C 10 carbocyclyl and 3-12 membered heterocyclyl is optionally substituted with one or more groups R b .

15. The compound of claim 1 wherein one R e taken together with R 3 and the atoms to which they are attached form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxy, C 1-6 alkoxy and C 3 -C 10 carbocyclyl.

16. The compound of claim 1 wherein one R e taken together with R 3 and the atoms to which they are attached form an azetidine ring, which ring is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxy, C 1-6 alkoxy and C 3 -C 10 carbocyclyl.

17. The compound of claim 1 wherein one R e taken together with R 4 and the atoms to which they are attached form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxy, C 1-6 alkoxy and C 3 -C 10 carbocyclyl.

18. The compound of claim 1 wherein one R e taken together with R 4 and the atoms to which they are attached form a 3-12 membered heterocyclyl that includes 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur that is selected from the group consisting of pyrrolidine, piperidine, and azepane, which 3-12 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 alkoxy is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxy, C 1-6 alkoxy and C 3 -C 10 carbocyclyl.

19. The compound of claim 1 wherein the group:

is selected from the group consisting of:

20. The compound of claim 1 wherein the group:

is selected from the group consisting of:

21. The compound of claim 1 wherein the group:

is selected from the group consisting of:

22. A compound selected from the group consisting of:

or a salt thereof.

23. A composition comprising a compound of formula (I) as described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle.