TEAD inhibitors and uses thereof

1. A compound of Formula I′:

or a pharmaceutically acceptable salt thereof, wherein:

L 1 is C 1-6 bivalent straight or branched hydrocarbon chain wherein 1, 2, or 3 methylene units of the chain are independently and optionally replaced with —O—, —CH(OR)—, —CH(SR)—, —CH(N(R) 2 )—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)—, —C(O)N(R)—, —(R)NC(O)—, —OC(O)N(R)—, —(R)NC(O)O—, —N(R)C(O)N(R)—, —S—, —SO—, —SO 2 N(R)—, —(R)NSO 2 —, —C(S)—, —C(S)O—, —OC(S)—, —C(S)N(R)—, —(R)NC(S)—, or —(R)NC(S)N(R)—;

Ring A is optionally substituted phenyl;

Ring B is optionally substituted

R w is -L-Y;

L is a covalent bond or a bivalent C 1-8 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one, two, or three methylene units of L are optionally and independently replaced by cyclopropylene, —NR—, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO 2 —, —SO 2 N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO 2 —, —C(═S)—, —C(═NR)—, —N═N—, or —C(═N 2 )—;

Y is hydrogen, C 1-6 aliphatic optionally substituted with oxo, halogen, NO 2 —, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 R e groups;

each R e is independently selected from -Q-Z, oxo, NO 2 —, halogen, CN, or a C 1-6 aliphatic optionally substituted with oxo, halogen, NO 2 , or CN;

Q is a covalent bond or a bivalent C 1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —SO—, or —SO 2 —, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO 2 —, or —SO 2 N(R)—;

Z is hydrogen or C 1-6 aliphatic optionally substituted with oxo, halogen, NO 2 , or CN; 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 C 1-6 bivalent straight or branched hydrocarbon chain wherein 1, 2, or 3 methylene units of the chain are independently replaced with —O—, —CH(OR)—, —CH(N(R) 2 )—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)—, —C(O)N(R)—, —(R)NC(O)—, —OC(O)N(R)—, —(R)NC(O)O—, or —N(R)C(O)N(R)—.

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein L 1 is —CH 2 —.

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

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein Ring A is

R 1 is hydrogen, and R 7 is —C 1-6 aliphatic substituted 0-6 times by halogen.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Ring B is

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein Ring B is

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

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (IX) or (X):

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (IXa), (IXb), or (Xa):

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XII):

12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIIa):

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIII) or (XIV):

14. The compound of claim 13 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XIIIa) or (XIIIb):

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XV):

16. The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (XVa) or (XVb):

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

18. The compound of claim 1 , which is selected from:

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein L 1 is C 1-6 bivalent straight or branched hydrocarbon chain wherein 1, 2, or 3 methylene units of the chain are independently replaced with —N(R)—.

20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 is —CH 2 —, —CH(CH 3 )—, —NH—CH 2 —, —NH—CH(CH 3 )—, —C(O)—NH—, or —N(CH 3 )—,

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is

wherein each of R 1 and R 7 is independently —H, -halogen, —CN, —NO 2 —, —C 1-6 aliphatic, or —O—C 1-6 aliphatic, wherein each of —C 1-6 aliphatic and —O—C 1-6 aliphatic is independently substituted 0, 1, 2, 3, 4, 5, or 6 times by -halogen, —CN, or —NO 2 .

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

L is —NRC(O)CH═CH—, —NRC(O)CH═CHCH 2 N(CH 3 )—, —NRC(O)CH═CHCH 2 O—, —CH 2 NRC(O)CH═CH—, —NRSO 2 CH═CH—, —NRSO 2 CH═CHCH 2 —, —NRC(O)(C═N 2 )—, —NRC(O)(C═N 2 )C(O)—, —NRC(O)CH═CHCH 2 N(CH 3 )—, —NRSO 2 CH═CH—, —NRSO 2 CH═CHCH 2 —, —NRC(O)CH═CHCH 2 O—, —NRC(O)C(═CH 2 )CH 2 —, —CH 2 NRC(O)—, —CH 2 NRC(O)CH═CH—, —CH 2 CH 2 NRC(O)—, or —CH 2 NRC(O)cyclopropylene-; and

Y is hydrogen or C 1-6 aliphatic optionally substituted with oxo, halogen, NO 2 —, or CN.

24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

L is a covalent bond;

Y is a partially unsaturated 4-6 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with 1-4 R e groups; and

each R e is independently selected from oxo, NO 2 —, halogen, and CN.