Tead inhibitors and uses thereof

A compound of Formula I′

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is C—Rx1 or N;
• X2 is C—Rx2 or N;
• X3 is C—Rx3 or N;
• X4 is C—Rx4 or N;
• X6 is C—Rx6 or N;
• wherein no more than three of X1, X2, X3, X4, or X6 are N;
• each Rx1, Rx2, Rx3, Rx4, Rx5, and Rx6 is independently selected from hydrogen, —CN, halogen, —OR, —N(R)2, or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each R is independently hydrogen or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• L1 is —C(O)N(R2)—*, —S(O)2—*, —S(O)2N(R2)—*, or —C(O)O—*, wherein * represents the point of attachment to R1;
• R1 is hydrogen or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• R2 is hydrogen or an optionally substituted C1-6 aliphatic;
• or
• R1 and R2, together with their intervening atoms, may form an optionally substituted 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms atoms independently selected from nitrogen, oxygen, and sulfur;
• each L3 is independently a covalent bond, —O—, or —NR—;
• each R3 is independently selected from hydrogen, halogen, or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• R4 is —CN or C1-6 aliphatic optionally substituted with —OR;
• and
• m is 0-4.

A compound of Formula I″:

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is C—Rx1 or N;
• X2 is C—Rx2 or N;
• X3 is C—Rx3 or N;
• X4 is C—Rx4 or N;
• wherein no more than two of X1, X2, X3, or X4 are N;
• each Rx1, Rx2, Rx3, and Rx4 is independently selected from hydrogen, —CN, halogen, —OR, —N(R)2, or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• Rx5′ is selected from —CN, halogen, —OR, —N(R)2, or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur
• each R is independently hydrogen or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• L1 is —C(O)N(R2)—*, —S(O)2—*, —S(O)2N(R2)—*, or —C(O)O—*, wherein * represents the point of attachment to R1;
• R1 is hydrogen or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• R2 is hydrogen or an optionally substituted C1-6 aliphatic;
• or
• R1 and R2, together with their intervening atoms, may form an optionally substituted 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms atoms independently selected from nitrogen, oxygen, and sulfur;
• each L3 is independently a covalent bond, —O—, or —NR—;
• and
• each R3 is independently selected from hydrogen, halogen, or an optionally substituted group selected from the group consisting of C1-6 aliphatic, phenyl, a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, and a 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.