GCN2 inhibitors and uses thereof
The present invention provides compounds inhibiting General amino acid Control Non-derepressible 2 kinase (“GCN2”), compositions thereof, and methods of using the same for treating various disorders, such as cancer.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
Ring A is a 4-8 membered saturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
Ring B is
Ring C is
each of R 1 is independently fluoro, methyl, ethyl, —OH, methoxy, —CH 2 OH,
each of R 2 is independently
R 3 is hydrogen;
R 4 is hydrogen;
m is 0, 1, 2, 3, 4 or 5;
n is 0, 1, or 2;
p is 0 or 1; and
q is 0 or 1.
2. The compound of claim 1 , of one of formula X-a, X-b, or X-c:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein m is 1, 2, 3, or 4.
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 Ring A is:
6. The compound of claim 1 , wherein each of R 1 is independently fluoro, methyl, ethyl,
7. The compound of claim 1 , wherein each of R 1 is independently fluoro, methyl,
8. The compound of claim 1 wherein each of R 1 is independently fluoro, methyl,
9. The compound of claim 1 , wherein Ring A is
10. The compound of claim 1 , wherein each of R 2 is independently
11. The compound of claim 1 , wherein each of R 2 is independently —CHF 2 , —CF 3 , or —CF 2 CH 3 .
12. The compound of claim 1 , wherein Ring B is
13. The compound of claim 1 , wherein m is 3.
14. The compound of claim 1 , wherein n is 1.
15. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising a compound according to claim 15 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
17. The compound of claim 1 , wherein Ring A is a 5-7 membered saturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
18. The compound of claim 1 , wherein Ring A is
19. The compound of claim 1 , wherein Ring A is:
20. The compound of claim 1 , wherein Ring A is: