Inhibitors of kras g12c mutant proteins

A compound having the following structure (I):

• or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein:
• G1 and G2 are each independently N or CH;
• L is a bond, NR or alkylene;
• X is a bond or CH2 when G1 is N;
• or X is a bond, NR or O when G1 is CH;
• R is H or C1-C6 alkyl;
• R1 is aryl or heteroaryl;
• R2 is arylene or heteroarylene, wherein the aryl or heteroarylene is substituted with R5 and R6;
• R3a and R3b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl or aminocarbonyl;
• or one R3a and one R3b join to form a carbocyclic or heterocyclic ring, and each remaining R3a and R3b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl or aminocarbonyl;
• or one R3b joins with one R4b to form a carbocyclic or heterocyclic ring, and each R3a and each remaining R3b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminoalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• or one R3b joins with one of R5 or R6 to form a carbocyclic or heterocyclic ring, and each R3a and each remaining R3b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminoalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• R4a and R4b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl or aminocarbonyl;
• or one R4a and one R4b join to form a carbocyclic or heterocyclic ring, and each remaining R4a and R4b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl or aminocarbonyl;
• or one R4b joins with one R3b to form a carbocyclic or heterocyclic ring, and each R4a and each remaining R4b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 alkynyl, hydroxylalkyl, aminoalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• R5 and R6 are each independently H, —OH, —CN, halo, C1-C6 alkyl or aminocarbonyl;
• or one of R5 or R6 joins with one R3b to form a carbocyclic or heterocyclic ring, and the other of R5 or R6 is H, —OH, —CN, halo, C1-C6 alkyl or aminocarbonyl;
• m1 and m2 are each independently 1, 2 or 3;
• 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.