Inhibitors of RAS and methods of use thereof

A compound having one of the following structures (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Ibb), (Icc), (Idd), (Tee), (Iff), (Igg), (Ihh), (Iii) or (Ijj):

• or a pharmaceutically acceptable salt, isotopic form, stereoisomer or prodrug thereof, wherein:
• L is absent or a linker selected from the group consisting of —O—, —S—, —NRc—, —NRcC(═O)—, —NRcS(═O)2— and —S(═O)2—, wherein Rc is H or C1-C6 alkyl;
• L2 is a bond or alkylene;
• Q is —C(═O)—, —C(═NR7)—, —NR8C(═O)—, —S(═O)2— or —NR8S(═O)2—;
• R′ is H, C1-C6 alkyl, —CONRaRb, —C1-C6 alkylene-CONRaRb, C1-C6 haloalkyl, C1-C6 hydroxylalkyl, C1-C6 aminylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, aryl or heteroaryl, wherein Ra and Rb are independently H or C1-C6 alkyl;
• R1 is aryl, cycloalkyl, heterocyclyl or heteroaryl;
• R2a, R2b and R2c are independently H, amino, cyano, halo, hydroxyl, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy;
• C3-C8 cycloalkyl, heterocyclylalkyl, C2-C6 alkynyl, C2-C6 alkenyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, aminylcarbonyl, heteroaryl or aryl;
• R3a and R3b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkynyl, hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• or R3a and R3b join to form oxo, a carbocyclic ring or a heterocyclic ring;
• or R3a is H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkynyl, hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl, and R3b joins with R4b to form a carbocyclic or heterocyclic ring;
• R4a and R4b are, at each occurrence, independently H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkynyl, hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl;
• or R4a and R4b join to form oxo, a carbocyclic ring or a heterocyclic ring;
• or R4a is H, —OH, —NH2, —CO2H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkynyl, hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl, and R4b joins with R3b to form a carbocyclic or heterocyclic ring;
• when is a double bond then R5 and R6 are each independently H, halo, cyano, carboxyl, C1-C6 alkyl, alkoxycarbonyl, aminylalkyl, alkylaminylalkyl, aryl, heterocyclyl, heterocyclylalkyl, heteroaryl or hydroxylalkyl, or R5 and R6 join to form a carbocyclic, heterocyclic or heteroaryl ring;
• when is a triple bond then R5 is absent and R6 is H, C1-C6 alkyl, aminylalkyl, alkylaminylalkyl or hydroxylalkyl;
• R7 is H, —OH, —CN or C1-C6 alkyl;
• and
• R8 is H, C1-C6 alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, C3-C8 cycloalkyl or heterocyclylalkyl,
• wherein each alkyl, alkylene, haloalkyl, hydroxylalkyl, aminylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, alkylamino, alkoxy, haloalkoxy;
• heterocyclylalkyl, alkynyl, alkenyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, aminylcarbonyl and alkoxyalkyl, is independently optionally substituted with one or more substituents.