Spiros and related analogs for inhibiting YAP/TAZ-TEAD

A compound of Formula II, Formula III or Formula IV:

• or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
• R1 is
• substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of:
• (a) halogen,
• (b) cyano,
• (c) C1-C6 alkyl,
• (d) C3-C6 cycloalkyl,
• (e) C1-C6 haloalkyl,
• (f) —OZ1, and
• (g) unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C1-C6 haloalkyl, and —OZ1,
• Y is N—;
• R2 and R3 are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• or
• R2 and R3 taken together with the carbon atom to which they are attached form a —C(═O)— group;
• R4 is selected from the group consisting of:
• (i) hydrogen,
• (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
• (a) halogen,
• (b) hydroxy,
• (c) cyano,
• (d) —OZ1,
• (e) —SZ1,
• (iii) —C(═O)Z2
• (iv) —C(═O)OZ2,
• (v) —C(═O)NZ3Z4,
• R5 is selected from the group consisting of hydrogen and C1-C6 alkyl;
• R6 is selected from the group consisting of:
• (i) —C(═O)Z2,
• (ii) —C(═O)NZ3Z4,
• (iii) —S(═O)2Z8, and
• (iv) —S(═O)2NZ3Z4;
• each Z1 is independently selected from the group consisting of:
• (i) hydrogen,
• (ii) C1-C6 alkyl,
• (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z8, —S(═O)2NZ3Z4, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ3Z4 and 4- to 8-membered heterocycle,
• (iv) C2-C6 alkynyl,
• (v) C3-C6 cycloalkyl,
• (vi) C3-C6 cycloalkenyl, and
• (vii) C1-C6 haloalkyl;
• each Z2 is independently selected from the group consisting of:
• (i) C1-C6 alkyl,
• (ii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z8, —S(═O)2NZ3Z4, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ3Z4 and 4- to 8-membered heterocycle,
• (iii) C2-C6 alkynyl,
• (iv) C3-C6 cycloalkyl,
• (v) C3-C6 cycloalkenyl, and
• (vi) C1-C6 haloalkyl;
• each Z3 is independently selected from the group consisting of:
• (i) hydrogen;
• (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z8, halogen, heteroaryl, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of 4- to 8-membered heterocycle,
• (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z8, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of 4- to 8-membered heterocycle,
• (iv) C2-C6 alkynyl,
• (v) C3-C6 cycloalkyl,
• (vi) C3-C6 cycloalkenyl, and
• (vii) C1-C6 haloalkyl;
• each Z4 is independently selected from the group consisting of:
• (i) hydrogen,
• (ii) C1-C6 alkyl, and
• (iii) C3-C6 cycloalkyl;
• each Z8 is independently selected from the group consisting of:
• (i) hydrogen,
• (ii) C1-C6 alkyl,
• (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of 4- to 8-membered heterocycle,
• (iv) halogen, and
• (v) hydroxy;
• X is ═CR7a—;
• X1 is ═CR7b—;
• X2 is ═CR7c—;
• X3 is selected from the group consisting of ═N— and ═CR7d—;
• and
• R7a, Rb, R7c and R7d, are independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, C1-C6 alkyl, C1-C6 haloalkyl, —OZ1, and —NZ3Z4.