GAS41 inhibitors and methods of use thereof

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, hydroxy, alkoxy, thioalkyl, halogen, haloalkyl, carboxy, acyl, amido, cyano, and sulfonyl;

X is —C(O)—, —C(S)—, —CH 2 —, or —SO 2 —, or is absent;

Y is —NR a —;

R a is selected from hydrogen, alkyl, haloalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, and aminoalkyl, or R a is taken together with the nitrogen atom to which it is attached to form a fused ring with A, or R a and R 1 together with the atoms to which they are attached together form an optionally substituted heterocyclic ring;

Z is absent or is —CR b R c —;

R b and R c are each independently selected from hydrogen and alkyl;

A is a five-membered heteroaryl;

Q is a four-, five-, or six-membered heterocyclyl;

R 2 is selected from hydrogen, halo, alkyl, amino, and hydroxy; and

R 3 is a group of formula:

wherein: B is a 5-membered monocyclic heteroaryl having 1 or 2 heteroatoms independently selected from N and S; J is absent; C is selected from aryl, heteroaryl, and heterocyclyl; m is 0 or 1; n is 0, 1, 2, or 3; R g is C 1 -C 6 alkyl; and each R h is independently selected from alkyl, halo, haloalkyl, amino, aminoalkyl, amido, amidoalkyl, sulfonamido, sulfonamidoalkyl, acyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, and cycloalkylalkyl;

wherein each alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, heterocyclyl, and heterocyclylalkyl is independently optionally substituted with 1, 2, 3, 4, or 5 substituents,

with the proviso that when Z is —CR b R c —, R 1 is not cycloalkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is a monocyclic heterocyclyl having 1 or 2 heteroatoms independently selected from N, O, and S.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —C(O)—.

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

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is absent.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is a five-membered heteroaryl having 1, 2, or 3 heteroatoms independently selected from N, O, and S.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from thiophene and thiazole.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q is selected from azetidine, pyrrolidine, and piperidine.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the group

a formula selected from:

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has formula (Ia):

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has formula (Ib):

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has formula (Ic):

wherein:

n is 0, 1, 2 or 3; and

each R h is independently selected from C 1 -C 6 alkyl, halo, halo-C 1 -C 6 -alkyl, amino, amino-C 1 -C 6 -alkyl, hydroxy, hydroxy-C 1 -C 6 -alkyl, C 1 -C 6 alkoxy, amido, amido-C 1 -C 6 -alkyl, acyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, heterocyclyl, heterocyclyl-C 1 -C 6 -alkyl, cycloalkyl, and cycloalkyl-C 1 -C 6 -alkyl.

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

15. The compound of claim 1 , wherein the compound is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.