Heterocyclic compounds and uses thereof

A compound of the formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• W6 is selected from C(R6) and N;
• R6 is selected from hydrogen, halogen, —CN, and C1-6haloalkyl;
• R8 is selected from hydrogen and halogen;
• R17 is selected from C6-10aryl and 5-10 membered heteroaryl, each of which is optionally substituted with one or more R20q;
• each Rz1 is independently selected from hydrogen, halogen, —CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are optionally substituted with one, two, or three R20z1;
• each R20z1 is independently selected from halogen, oxo, —CN, —OR12, and —N(R12)(R13);
• is selected from
• one Rz5, R20z, or R20zz is E, wherein E is a moiety capable of covalently binding to a Ras mutant protein at an amino acid corresponding to G12D or G12S of human K-Ras mutant G12D or G12S protein, respectively;
• each Rz4 is hydrogen;
• and each Rz5 is independently selected from E, hydrogen, —C(O)R12, and —N(R14)C(O)R12;
• wherein one Rz4 and one Rz5 may join to form monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic 3-7 membered heterocycloalkyl is optionally substituted with one, two, or three R20z;
• each R12 is independently selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, —CH2—C1-9heteroaryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, —CH2—C1-9heteroaryl, and C1-9heteroaryl are optionally substituted with one, two, or three R20l;
• R12a is selected from —C(R12c)2—C3-10cycloalkyl and —C(R12c)2—C2-9heterocycloalkyl, wherein —C(R12c)2—C3-10cycloalkyl and —C(R12c)2—C2-9heterocycloalkyl are optionally substituted with one, two, or three R20l;
• each R12c is independently selected from hydrogen and R20lc;
• each R13 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• or R12 and R13 together with the nitrogen to which they are attached, form a C2-9heterocycloalkyl ring optionally substituted with one, two, or three R20m;
• each R14 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• each R15 is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three R20o;
• each R20z is independently selected from E, halogen, oxo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR12, —SR12, —N(R12)(R13), —C(O)OR12, —OC(O)N(R12)(R13), —N(R14)C(O)N(R12)(R13), —N(R14)C(O)OR15, —N(R14)S(O)2R15, —C(O)R12, —S(O)R15, —OC(O)R15, —C(O)N(R12)(R13), —C(O)C(O)N(R12)(R13), —N(R14)C(O)R12, —S(O)2R15, —S(O)2N(R12)(R13), —S(═O)(═NH)N(R12)(R13), —CH2C(O)N(R12)(R13), —CH2N(R14)C(O)R15, —CH2S(O)2R15, and —CH2S(O)2N(R12)(R13), wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three R20zz;
• each R20lc, R20l, R20m, R20o, and R20q is independently selected from halogen, oxo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, C1-9heteroaryl, —CH2—C1-9heteroaryl, —OR21, —SR21, —N(R22)(R23), —C(O)OR22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —OC(O)N(R22)(R23), —N(R24)C(O)N(R22)(R23), —N(R24)C(O)OR25, —N(R24)C(O)R21, —N(R24)S(O)2R25, —C(O)R21, —S(O)2R25, —S(O)2N(R22)(R23), —OCH2C(O)OR22, ═NR21, and —OC(O)R25;
• two R20q bonded to adjacent atoms optionally join to form C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, or C1-9heteroaryl;
• wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, C1-9heteroaryl, and —CH2—C1-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, —CN, C1-6alkyl, C1-6 haloalkyl, C1-6alkoxy, C1-6haloalkoxy, —OR21, —SR21, —N(R22)(R23), —C(O)OR22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —OC(O)N(R22)(R23), —N(R24)C(O)N(R22)(R23), —N(R24)C(O)OR25, —N(R24)C(O)R25, —N(R24)S(O)2R25, —C(O)R25, —S(O)2R25, —S(O)2N(R22)(R23), and —OC(O)R25;
• each R20zz is independently selected from E, halogen, oxo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, C1-9heteroaryl, —CH2—C1-9heteroaryl, —OR21, —SR21, —N(R22)(R23), —C(O)OR22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —OC(O)N(R22)(R23), —N(R24)C(O)N(R22)(R23), —N(R24)C(O)OR25, —N(R24)C(O)R21, —N(R24)S(O)2R25, —C(O)R21, —S(O)2R25, —S(O)2N(R22)(R23), —OCH2C(O)OR22, ═NR21, and —OC(O)R25;
• wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, C1-9heteroaryl, and —CH2—C1-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, —CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, —OR21, —SR21, —N(R22)(R23), —C(O)OR22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —OC(O)N(R22)(R23), —N(R24)C(O)N(R22)(R23), —N(R24)C(O)OR25, —N(R24)C(O)R25, —N(R24)S(O)2R25, —C(O)R25, —S(O)2R25, —S(O)2N(R22)(R23), and —OC(O)R25;
• each R21 and R22 is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• each R23 and R24 is independently selected from hydrogen and C1-6alkyl;
• and
• each R25 is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl.