Covalent inhibitors of K-Ras G12C

A compound having the following structure (V):

• or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:
• R1 is aryl or heteroaryl;
• R30a and R30b are, at each occurrence, independently H, —OH, —NH2, —CO2H, cyano, cyanoalkyl, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl;
• or R30a and R30b join to form a carbocyclic or heterocyclic ring;
• or R30a is H, —OH, —NH2, —CO2H, cyano, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl and R30b joins with R31b to form a carbocyclic or heterocyclic ring;
• R31a and R31b are, at each occurrence, independently H, —OH, —NH2, —CO2H, cyano, cyanoalkyl, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl;
• or R31a and R31b join to form a carbocyclic or heterocyclic ring;
• or R31a is H, —OH, —NH2, —CO2H, cyano, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl and R31b joins with R30b to form a carbocyclic or heterocyclic ring;
• R32a and R32b are, at each occurrence, independently H, —OH, —NH2, —CO2H, cyano, cyanoalkyl, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl;
• or R32a and R32b join to form a carbocyclic or heterocyclic ring;
• or R32a is H, —OH, —NH2, —CO2H, cyano, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl and R32b joins with R33b to form a carbocyclic or heterocyclic ring;
• R33a and R33b are, at each occurrence, independently H, —OH, —NH2, —CO2H, cyano, cyanoalkyl, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl;
• or R33a and R33b join to form a carbocyclic or heterocyclic ring;
• or R33a is H, —OH, —NH2, —CO2H, cyano, C1-C6alkyl, C3-C8cycloalkyl, hydroxylalkyl, aminoalkyl, carboxylalkyl or aminocarbonyl and R33b joins with R32b to form a carbocyclic or heterocyclic ring;
• L1 is carbonyl, —NHC(═O)—, alkylene, alkenylene, alkylenecarbonyl or alkenylenecarbonyl;
• L2 is a bond or alkylene;
• G1, G2, G3 and G4 are each independently N or CR, where R is H, cyano, halo or C1-C6alkyl;
• n1, n2, n3 and n4 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 K-Ras, H-Ras or N-Ras G12C mutant protein.