Epoxyamides as kras g12c and kras g12d inhibitors and methods of using the same

A compound having a structure of formula (I)

• wherein
• R1 is H, halo, or —CH3;
• R2 is H, halo, or —CH3;
• R3 is
• b is optionally a single or a double bond;
• ring A is a monocyclic 4-7 membered ring or a bicyclic, bridged, fused, or spiro 6-11 membered ring;
• L is a bond or NR4;
• R4 is H, —C1-6alkyl, —C2-6alkynyl, C1-6 alkylene-O—C1-4alkyl, C1-6alkylene-OH, C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OH, —C(O)OC1-4alkyl, —C1-6 alkylene-O-aryl, —N═N, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, or —C0-3alkylene-C2-14heteroaryl;
• R5 is H, halo, an —C1-6alkyl, —C2-6alkynyl, —C0-6 alkylene-O—C1-6alkyl, —C1-6 alkylene-O—C1-4alkyl, —C1-6alkylene-OH, —C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OH, —C(O)OC1-4alkyl, —C0-6 alkylene-O—C6-14aryl, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, —C0-3alkylene-C2-14heteroaryl, or cyano;
• R5a is selected from H, —C1-6alkyl, —C2-6alkynyl, —C1-6 alkylene-O—C1-4alkyl, —C1-6alkylene-OH, —C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OH, —C(O)OC1-4alkyl, , —C0-6 alkylene-O—C6-14aryl, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, or —C0-3alkylene-C2-14heteroaryl;
• R5b is selected from H, —C1-6alkyl, —C2-6alkynyl, —C1-6 alkylene-O—C1-4alkyl, —C1-6alkylene-OH, —C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OH, —C(O)OC1-4alkyl, , —C0-6 alkylene-O—C6-14aryl, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, or —C0-3alkylene-C2-14heteroaryl;
• or R5a and R5b together, may represent an ═O or ═N═N;
• R6 is H, halo, —C1-6alkyl, —C2-6alkynyl, —C1-6 alkylene-O—C1-4alkyl, —C1-6alkylene-OH, —C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OH, —C(O)OC1-4alkyl, , —C0-6 alkylene-O—C6-14aryl, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, or —C0-3alkylene-C2-14heteroaryl;
• R5a and R6a, together with the atoms to which they are attached, may form a 3-6 membered ring that optionally includes one or two heteroatoms selected from 0, S or N;
• or
• R5a and R6a are absent when b is a double bond;
• R6A is H, or —C1-6alkyl;
• R6b is H, —C1-6alkyl, —C2-6alkynyl, —C1-6 alkylene-O—C1-4alkyl, —C1-6alkylene-OH, —C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OH, —C(O)OC1-4alkyl, —C0-6 alkylene-O—C6-14aryl, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, —C0-3alkylene-C2-14heteroaryl, or cyano;
• or R6a and R6b together, may represent an ═0;
• R7 is H or C1-8alkyl;
• R8 is H, OH, NRaRb;
• wherein Ra and Rb are each independently H, halo, —C1-6alkyl, —C2-6alkynyl;
• wherein the ring A or the —C1-6alkyl, —C2-6alkynyl, —C1-6 alkylene-O—C1-4alkyl, —C1-6alkylene-OH, —C1-6haloalkyl, —C1-6alkyleneamine, —C0-6 alkylene-amide, —C(O)OC1-4alkyl, —C1-6 alkylene-O-aryl, —C0-3alkylene-C(O)C1-4alkylene-OH, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C0-3alkylene-C3-14cycloalkyl, —C0-3alkylene-C2-14heterocycloalkyl, —C0-3alkylene-C6-14aryl, or —C0-3alkylene-C2-14heteroaryl groups of any of the R4, R5, R1a, R51, R6, R6a, R6b, R7 and R8 may be unsubstituted or substituted with 1, 2, 3, or 4 substituents, as allowed, independently selected from halo, —C1-6alkyl, —O—C1-6alkyl, —OH, or —C1-6alkyl-CN;
• or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.