Fused n-heterocyclic compounds and methods of use thereof

A compound having the following structure (I):

• or a pharmaceutically acceptable salt, isotopic form, stereoisomer or prodrug thereof, wherein:
• A is a five or six-membered, nitrogen containing heterocyclyl or heteroaryl substituted with -L-R1 and optionally substituted with 1, 2 or 3 additional substituents selected from the group consisting of R2a, R2b and R2c;
• B is C or N;
• Ra, Rb and Rc are, at each occurrence, independently H, amino, cyano, halo, hydroxyl, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy;
• C3-C8 cycloalkyl, heterocycylalkyl, C1-C6 alkynyl, C1-C6 alkenyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, aminylcarbonyl, heteroaryl or aryl;
• R1 is cycloalkyl, heterocyclyl, aryl or heteroaryl;
• R2a, R2b and R2c are, at each occurrence, independently H, amino, cyano, halo, hydroxyl, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy;
• C3-C8 cycloalkyl, heterocycylalkyl, C1-C6 alkynyl, C1-C6 alkenyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, aminylcarbonyl, heteroaryl or aryl;
• L is, at each occurrence, independently absent or a linker selected from the group consisting of —O—, —NRd—, —NRdC(═O)—, —NRdS(═O)2— and —S(═O)2—, wherein Rd is H or C1-C6 alkyl;
• L1 is alkylene, heteroalkylene, heterocyclylene, aminylheterocyclylene alkylheterocyclylene or heteroalkylheterocyclylene;
• indicates an aromatic ring;
• and
• E is an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS, HRAS or NRAS G12C mutant protein.