Tead inhibitors and uses thereof
The present invention provides compounds, compositions thereof, and methods of using the same.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
L 1 is —NH—CH 2 — or —NH—C(O)—;
Ring A is phenyl, optionally substituted 1-2 times by halogen, —CN, —NO 2 , or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ;
R 2 is an optionally substituted 5-membered heteroaryl ring having 2 nitrogen atoms;
R 3 is —H;
R 4 is halogen, —S(O) 2 N(R) 2 , —S(O)N(R) 2 , or —C(O)N(R) 2 ;
R 6 is —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 ; and
each R is independently —H or optionally substituted —C 1-6 aliphatic.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 is NH—CH 2 —.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, optionally substituted 1-2 times by —C 1-6 aliphatic substituted 0-6 times by halogen.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is
and R is unsubstituted —C 1-6 aliphatic.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is —S(O) 2 NHR.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is —H.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formulas (IXa-1), (IXa-2), (Xa-1), or (Xa-2):
wherein L 1 is —NH—CH 2 —, and each R is independently —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 .
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIa-1) or (XIa-2):
wherein L 1 is —NH—CH 2 —, and each R is independently —H or —C 1-6 aliphatic substituted 0-6 times by halogen, —CN, or —NO 2 .
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIIa-1) or (XIIa-2):
wherein L 1 is —NH—CH 2 —, and R is —C 1-3 aliphatic substituted 1, 2, 3, 4, 5, or 6 times by F.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIIIa-1) or (XIIIa-2):
wherein L 1 is —NH—CH 2 —, and R is optionally substituted —C 1-6 aliphatic.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIVa-1) or (XIVa-2):
wherein L 1 is —NH—CH 2 −.
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formulas (XVa-1), or (XVa 2):
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formulas (XVIa-1), or (XVIa 2):
14. The compound of claim 1 , which is selected from:
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
16. A pharmaceutical composition comprising the compound of claim 14 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (II):
wherein L 1 is —NH—CH 2 —, R 1 is —H, -halogen, —CN, —NO 2 , or —C 1-6 aliphatic, and R 7 is —H, -halogen, —CN, —NO 2 , or —C 1-6 aliphatic.
18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is
19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is —S(O) 2 NH—CH 3 .
20. A compound:
or a pharmaceutically acceptable salt thereof.
21. A pharmaceutical composition comprising the compound of claim 20 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
22. A compound:
or a pharmaceutically acceptable salt thereof.
23. A pharmaceutical composition comprising the compound of claim 22 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
24. A compound:
or a pharmaceutically acceptable salt thereof.
25. A pharmaceutical composition comprising the compound of claim 24 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
26. A compound:
or a pharmaceutically acceptable salt thereof.
27. A pharmaceutical composition comprising the compound of claim 26 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.