GCN2 inhibitors and uses thereof
The present invention provides compounds, compositions thereof, and methods of using the same.
1. A compound of one of formula XV-a, XV-a, or XV-c:
or a pharmaceutically acceptable salt thereof, wherein:
each of R 1 is independently hydrogen, halogen, —CN, —NO 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)NRS(O) 2 R, —C(O)N═S(O)R 2 , —NR 2 , —NRC(O)R, —NRC(O)NR 2 , —NRC(O)OR, —NRS(O) 2 R, —NRS(O) 2 NR 2 , —OR, —ON(R)SO 2 R, —P(O)R 2 , —SR, —S(O)R, —S(O) 2 R, —S(O)(NH)R, —S(O) 2 N(R) 2 , —S(NH 2 ) 2 (O)OH, —N═S(O)R 2 , —CH 3 , —CH 2 OH, —CH 2 NHSO 2 CH 3 , —CD 3 , —CD 2 NRS(O) 2 R, or R; or
two R 1 groups are optionally taken together to form ═O or ═NH; or
two R 1 groups are optionally taken together to form a bivalent C 2-4 alkylene chain;
each R is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
two R groups are optionally taken together to form a bivalent C 2-4 alkylene chain; or
two R groups are optionally taken together with their intervening atoms to form an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;
m is 0, 1, 2, 3, 4 or 5.
2. The compound of claim 1 , wherein m is 1, 2 or 3.
3. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
5. The compound of claim 1 , wherein R 1 is hydrogen, halogen, —CN, —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)NRS(O) 2 R, —C(O)N═S(O)R 2 , —NR 2 , —NRC(O)R, —NRC(O)NR 2 , —NRC(O)OR, —NRS(O) 2 R, —NRS(O) 2 NR 2 , —OR, —ON(R)SO 2 R, —P(O)R 2 , —SR, —S(O)R, —S(O) 2 R, —S(O)(NH)R, —S(O) 2 N(R) 2 , —S(NH 2 ) 2 (O)OH, —N═S(O)R 2 , —CH 3 , —CH 2 OH, —CH 2 NHSO 2 CH 3 , —CD 3 , —CD 2 NRS(O) 2 R, or R.
6. The compound of claim 1 , wherein two R 1 groups are taken together to form a bivalent C 2-4 alkylene chain.
7. The compound of claim 1 , wherein two R 1 groups are taken together to form ═O or ═NH.
8. The compound of claim 5 , wherein each R is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
9. The compound of claim 5 , wherein R is hydrogen.
10. The compound of claim 5 , wherein R is an optionally substituted C 1-6 aliphatic.
11. The compound of claim 5 , wherein R is an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring.
12. The compound of claim 5 , wherein R is an optionally substituted phenyl.
13. The compound of claim 5 , wherein R is an optionally substituted 8-10 membered bicyclic aromatic carbocyclic ring.
14. The compound of claim 5 , wherein R is an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
15. The compound of claim 5 , wherein R is an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
16. The compound of claim 5 , wherein R is an optionally substituted 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
17. The compound of claim 5 , wherein two R groups are taken together to form a bivalent C 2-4 alkylene chain.
18. The compound of claim 5 , wherein two R groups are taken together with their intervening atoms to form an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.
19. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of: fluoro, chloro, methyl, ethyl, —OH, —OCH 3 , —CH 2 OH, —CH 2 CN, —CF 3 , —CH 2 NH 2 , —COOH, —NH 2 ,
20. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
21. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
22. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
23. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
24. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
25. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
26. The compound of claim 1 , wherein a R 1 group is selected from the group consisting of:
27. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
28. A pharmaceutical composition comprising a compound according to claim 3 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.