Compounds and methods for yap/tead modulation and indications therefor

A compound of Formula (I):

• or a pharmaceutically acceptable salt, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein:
• Y1 is -Q-R1 and Y2 is R2;
• or
• Y1 is R2 and Y2 is -Q-R1;
• wherein Q is a bond or —O—;
• R1 is phenyl substituted with 0-4 G groups;
• each G is independently selected from halogen, OH, CN, alkyl optionally substituted with one or more R5, and alkoxy optionally substituted with one or more R5;
• each R2 is independently H, halogen, —C(O)O-alkyl, or C1-C3alkyl optionally substituted with 1-3 halogens, provided that not more than one R2 is —C(O)O-alkyl;
• R3 is H;
• halogen;
• alkenyl optionally substituted with cycloalkyl or heterocycloalkyl;
• heterocycloalkyl optionally substituted with —C(O)-alkyl;
• heterocycloalkenyl optionally substituted with C(O)-alkyl;
• heterocycloalkylalkyl optionally substituted with C(O)-alkyl;
• or heteroaryl optionally substituted with haloalkyl, cycloalkyl, or cycloalkylalkyl;
• R4 is H;
• alkyl;
• cycloalkyl optionally substituted with haloalkyl or —C(O)-alkenyl;
• heterocycloalkyl optionally substituted with —C(O)-alkyl, —C(O)-alkenyl, or —C(O)-cycloalkyl;
• or heterocycloalkylalkyl optionally substituted with —C(O)-alkyl, —C(O)—CH2—OH, or heteroaryl;
• R5 is halogen or OH;
• X is —(CH2)m—S(O)2—, —(CH2)n—C(O)—, or —C(O)O—, wherein the right-hand side indicates the point of attachment to Z;
• Z is —NR6R7, C1-C6alkyl optionally substituted with 1-4 R8, —C(CH3)═CH2, —CH2—CH═C═O, cycloalkyl optionally substituted with 1-4 R9, heterocycloalkyl optionally substituted with 1-4 R10, aryl optionally substituted with 1-4 R10, or heteroaryl optionally substituted with 1-4 R10;
• or X—Z is —C(═NR7)2—NR6R7;
• or X is a bond and Z is a 5-6 membered heteroaryl optionally substituted with CN, —C(O)—NR14R15, —S(O)2—C1-C3alkyl, or —SO2—NR14R15;
• R6 is hydrogen, —S(O)2—C1-C3alkyl, C1-C6alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each C1-C6alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with 1-3 R11;
• R7 is hydrogen or C1-C6alkyl;
• or
• R6 and R7, together with the nitrogen to which they are attached, form a heterocycloalkyl;
• R8 is —NR6R7, CN, hydroxy, alkoxy, haloalkoxy, —S—C1-C3alkyl, —S(O)—C1-C3alkyl, —S(O)2—C1-C3alkyl, —S(O)2—C1-C3haloalkyl, —S(O)2—NH2, —S(O)(NH)—C1-C3alkyl, —C(O)—NH2, —C(O)OH, —C(O)O—C1-C3alkyl, —C(O)C1-C3haloalkyl, —N(H)—C(O)—NR6R7, —N(H)—C(O)—C1-C3alkyl optionally substituted with —NR12R13 or CN, —N(H)—C(O)—C2-C6alkenyl, —N(H)—C(O)—C1-C3haloalkyl, —N(H)—C(O)O—C1-C6alkyl, —N(H)—C(NH)—NH2, —N(H)—S(O)2—NR12R13, —N(R7)—S(O)2—C1-C3alkyl, —N(R7)—S(O)2-cycloalkyl, —N(H)—S(O)2—C1-C3haloalkyl, —P(O)(OH)2, —P(O)(C1-C6alkyl)2, cycloalkyl optionally substituted with 1-3 R10, heterocycloalkyl optionally substituted with 1-3 R10, or heteroaryl optionally substituted with 1-3 R10;
• or
• two R8, together with the carbon atom to which they are attached, join together to form a cycloalkyl;
• each R9 is independently CN, —S(O)2—C1-C3alkyl, or —N(C1-3alkyl)2;
• each R10 is independently hydroxy, CN, C1-C6alkyl, haloalkyl, —NH2, —C(O)-alkenyl, —C(O)—NH2, —C(O)O-alkyl, —NH—C(O)-alkenyl, —S(O)2—C1-C3alkyl, —S(O)2—C2-C6alkenyl, or —S(O)2—NH2;
• each R11 is independently hydroxy, CN, alkoxy, —S(O)2—C1-C3alkyl, or cycloalkyl;
• each R12 and R13 are independently hydrogen, C1-C6alkyl, or C3-C6cycloalkyl;
• each R14 and R15 are independently hydrogen or C1-C6alkyl;
• n is 0, 1, or 2;
• and
• m is 0, 1, 2, or 3;
• provided that:
• if Z is —C(CH3)═CH2, then X is —C(O)O— or n is 1 or 2 or m is 1, 2, or 3;
• if X—Z is —C(O)—C1 alkyl, R8 cannot be CN, hydroxy, alkoxy, or haloalkoxy;
• if X is —C(O)—, then Z cannot be oxiranyl;
• if X is —C(O)— or —S(O)2—, Z is cycloalkyl substituted with one R9, and R9 is CN, then R9 cannot be attached to the same ring atom of Z as the atom to which X is attached;
• if X is —C(O)— or —S(O)2—, Z is heterocycloalkyl substituted with one R10, and R10 is hydroxy or CN, then R10 cannot be attached to the same ring atom of Z as the atom to which X is attached;
• and
• if X is —C(O)— or —S(O)2—, and Z is a partially saturated cycloalkyl or partially saturated heterocycloalkyl, a point of saturation of Z cannot be adjacent to X.