Substituted quinazolines as inhibitors of KRAS G12C

A compound having the following structure (I):

• or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein:
• represents a double or triple bond;
• Q is —C(═O)—, —C(═NR8′)—, —NR8C(═O)—, —S(═O)2— or —NR8S(═O)2—;
• Y is CR6;
• X is N;
• Z is N;
• L1 is a bond;
• L2 is a bond or alkylene;
• R′ is R1 and R″ is R2c;
• or R′ is H and R″ is R1;
• R1 is heterocyclyl, heteroaryl or aryl;
• R2a, R2b and R2c are each independently H, halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C8 cycloalkyl, heteroaryl or aryl;
• R3a and R3b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C2-C6 alkynyl, hydroxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• R4a and R4b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C2-C6 alkynyl, hydroxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• R6 is H, cyano, cyanoalkyl, amino, aminylalkyl, aminylalkylaminyl, aminylcarbonyl, aminylsulfonyl, —CO2NRaRb, alkylaminyl, haloalkylaminyl, hydroxyalkylaminyl, amidinylalkyl, amidinylalkoxy, amidinylalkylaminyl, guanidinylalkyl, guanidinylalkoxy, guanidinylalkylaminyl, C1-C6 alkoxy, aminylalkoxy, alkylaminylalkoxy, alkylcarbonylaminylalkoxy, C1-C6 alkyl, heterocyclyl, heterocyclyloxy, heterocyclylalkyloxy, heterocyclylaminyl, heterocyclylalkylaminyl, heteroaryl, heteroaryloxy, heteroarylalkyloxy, heteroarylaminyl, heteroarylalkylaminyl, aryl, aryloxy, arylaminyl, arylalkylaminyl or arylalkyloxy;
• Ra and Rb are each independently H or C1-C6 alkyl;
• or
• Ra and Rb join to form a carbocyclic or heterocyclic ring;
• R8 is H, C1-C6 alkyl or hydroxyalkyl;
• R8′ is H, —OH, cyano or C1-C6 alkyl;
• indicates a double bond;
• when is a double bond then R9 and R10 are each independently H, cyano, carboxy, C1-C6 alkyl, alkoxycarbonyl, aminylalkyl, alkylaminylalkyl, heteroaryl or hydroxyalkyl or R9 and R10 join to form a carbocyclic or heterocyclic ring;
• and
• when is a triple bond then R9 is absent and R10 is H, C1-C6 alkyl, aminylalkyl, alkylaminylalkyl or hydroxyalkyl,
• provided that at least one of R2a, R2b or R2c is not H when R1 is pyridyl, and wherein each alkylene, heterocyclyl, heteroaryl, aryl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, alkoxycarbonyl, C3-C8 cycloalkyl, C2-C6 alkynyl, hydroxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, aminylcarbonyl, aminylalkylaminyl, aminylcarbonyl, aminylsulfonyl, carbocyclic ring, heterocyclic ring, alkylaminyl, haloalkylaminyl, hydroxyalkylaminyl, amidinylalkyl, amidinylalkoxy, amidinylalkylaminyl, quanidinylalkyl, guanidinylalkoxy, guanidinylalkylaminyl, aminylalkoxy, alkylaminylalkoxy, alkylcarbonylaminylalkoxy, heterocyclyloxy, heterocyclylalkyloxy, heterocyclylaminyl, heterocyclylalkylaminyl, heteroaryloxy, heteroarylalkyloxy, heteroarylaminyl, heteroarylalkylaminyl, aryloxy, arylaminyl, arylalkylaminyl and arylalkyloxy is optionally substituted with one or more substituents selected from the group consisting of aminyl, cyano, hydroxy, imino, nitro, oxo, thioxo, halo, aminylsulfonyl, aminylcarbonyl, C1-C12 alkyl, C1-C6 alkylaminylcarbonyl, aminylcarbonylC1-C6 alkyl, C1-C12 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkoxyalkyl, C1-C6 haloalkoxyalkyl, cyanoC1-C6 alkyl, C1-C6 alkylcycloalkyl, C1-C6 alkylhetercycloalkyl, C2-C6 alkynyl, C1-C6 alkylaminyl, C1-C6 alkylcarbonylaminyl, C1-C6 hydroxyalkyl, C2-C6 alkenylcarbonylaminyl, C1-C6 thioalkyl, aryl, aralkyl, C3-C8 cycloalkyl optionally substituted with cyano, C3-C8 cycloalkylalkyl, aminylcarbonylC3-C8 cycloalkyl, C3-C8 cycloalkylaminylcarbonyl, C3-C8 fused cycloalkyl, heterocycyl, N-heterocyclyl, heterocyclylalkyl, heteroaryl, N-heteroaryl and heteroarylalkyl.