Substituted quinolines as inhibitors of KRAS G12C

A compound having the following structure (I′) or (I″):

• or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof,
• wherein:
• is a double or triple bond;
• Q is —C(═O)—, —C(═NR8′)—, —NR8C(═O)—, —S(═O)2— or —NR8S(═O)2—;
• W is CR6;
• X is CR6;
• Y is CR6;
• Z is N;
• L1 is a bond;
• L2 is a bond;
• R′ is R1 and R″ is R2c;
• or
• R′ is H and R″ is R1;
• R1 is heteroaryl;
• 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, CN, CO2H, halo, 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, CN, CO2H, halo, C1-C6 alkyl, C2-C6 alkynyl, hydroxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• R6 is, at each occurrence, independently H, CN, NH2, C1-C6 alkyl, C1-C6 alkoxy, CO2NRaRb, cyanoalkyl, aminylalkyl, aminylalkylaminyl, aminylcarbonyl, aminylsulfonyl, alkylaminyl, haloalkylaminyl, hydroxyalkylaminyl, amidinylalkyl, amidinylalkoxy, amidinylalkylaminyl, guanidinylalkyl, guanidinylalkoxy, guanidinylalkylaminyl, aminylalkoxy, alkylaminylalkoxy, alkylcarbonylaminylalkoxy, 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, together with the nitrogen atom to which they are attached, form a heterocyclyl;
• R8 is H, C1-C6 alkyl or hydroxyalkyl;
• R8′ is H, OH, CN or C1-C6 alkyl;
• R9 is H, CN, CO2H, C1-C6 alkyl, alkoxycarbonyl, aminylalkyl, alkylaminylalkyl, heteroaryl or hydroxyalkyl;
• and
• R10 is H, CN, CO2H, C1-C6 alkyl, alkoxycarbonyl, aminylalkyl, alkylaminylalkyl, heteroaryl or hydroxyalkyl;
• or
• R9 and R10, together with the carbon atoms to which they are attached, form a cycloalkenyl or heterocyclyl;
• wherein each 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, cycloalkenyl, heterocyclyl, alkylaminyl, haloalkylaminyl, hydroxyalkylaminyl, amidinylalkyl, amidinylalkoxy, amidinylalkylaminyl, guanidinylalkyl, 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 ═O, ═S, CN, OH, NO2, halo, aminyl, imino, aminylsulfonyl, aminylcarbonyl, C1-C12 alkyl, C1-C6 alkoxy, C1-C12 haloalkyl, C1-C6 alkylaminylcarbonyl, aminylcarbonylC1-C6 alkyl, C1-C6 haloalkoxy, C1-C6 alkoxyalkyl, C1-C6 haloalkoxyalkyl, cyanoC1-C6 alkyl, C1-C6 alkylcycloalkyl, C1-C6 alkylheterocycloalkyl, 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 CN, C3-C8 cycloalkylalkyl, aminylcarbonylC3-C8 cycloalkyl, C3-C8 cycloalkylaminylcarbonyl, C3-C8 fused cycloalkyl, heterocyclylalkyl, heteroarylalkyl, heterocyclyl and heteroaryl;
• provided that:
• (i) when is a triple bond, then R9 is absent and R10 is H, C1-C6 alkyl, aminylalkyl, alkylaminylalkyl or hydroxyalkyl;
• and
• (ii) when R1 is pyridyl, then at least one of R2a, R2b or R2c is not H.