Tead inhibitors and uses thereof
The present invention provides compounds, compositions thereof, and methods of using the same.
1. A method for treating mesothelioma in a patient, comprising administering to the patient 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 method of claim 1 , wherein L 1 is —NH—CH 2 —.
3. The method of claim 1 , wherein Ring A is phenyl, optionally substituted 1-2 times by —C 1-6 aliphatic substituted 0-6 times by halogen.
4. The method of claim 1 , wherein R 2 is
and R is unsubstituted —C 1-6 aliphatic.
5. The method of claim 1 , wherein R 1 is —S(O) 2 NHR.
6. The method of claim 1 , wherein R 6 is —H.
7. The method of claim 1 , 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 method of claim 1 , 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 method of claim 1 , 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 method of claim 1 , 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 method of claim 1 , wherein the compound is of Formula (XIVa-1) or (XIVa-2):
wherein L 1 is —NH—CH 2 —.
12. The method of claim 1 , wherein the compound is of Formulas (XVa-1), or (XVa-2):
13. The method of claim 1 , wherein the compound is of Formulas (XVIa-1), or (XVIa-2):
14. The method of claim 1 , wherein the compound is of Formula (II):
wherein L 1 is —NH—CH 2 —, le is —H, -halogen, —CN, —NO 2 , or —C 1-6 aliphatic, and R 7 is —H, -halogen, —CN, —NO 2 , or —C1-6 aliphatic.
15. The method of claim 1 , wherein R 2 is
16. The method of claim 1 , wherein R 4 is —S(O) 2 NH—CH 3 .
17. The method of claim 1 , wherein the compound is selected from:
or a pharmaceutically acceptable salt thereof.
18. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
19. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
20. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
21. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.