Irreversible inactivators targeting araf/mek complexes

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein
• each R2 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, halo, —CN, —OH, —NH2, —NH(C1-6 alkyl), and —N(C1-6 alkyl)2;
• n is 1 or 2;
• R1 is selected from the group consisting of
• L3 is selected from the group consisting of a bond, C1-C4 alkyl, and NH;
• each of RE1, RE2, and RE3 is independently selected from the group consisting of H, halo, —CN, and C1-C6 alkyl;
• a is 1 or 2;
• and
• each z is independently 0, 1, or 2, provided that the compound of Formula I is not

A compound of Formula II:

• or a pharmaceutically acceptable salt thereof;
• wherein
• A is N, CR3, or CR4;
• Rt is H or C1-6 alkyl;
• R2 is selected from the group consisting of H, halo, 6-10 membered aryl, 5-10 membered heteroaryl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 4-10 membered heterocycloalkyl, —OR6, —NR6R6, —SO2R6, —SO2NHR6, —NHSO2R6, —C(O)OR6, —C(O)NHR6, —C(O)R6, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein aryl, heteroaryl, heterocycloalkyl, cycloalkyl, alkyl, alkenyl, and alkynyl are optionally substituted one, two, or three times with R7;
• each R3 is independently selected from the group consisting of H, halo, C1-3 alkyl, C1-3 haloalkyl, and C1-3 alkoxy;
• and
• each R6 is independently selected from the group consisting of H, C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, C1-6 haloalkyl, 6-10 membered aryl, 5-6 membered heteroaryl, 3-6 membered cycloalkyl, and 3-6 membered heterocycloalkyl;
• each R7 is independently selected from the group consisting of halo, —OH, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, and —CN;
• R4 is selected from the group consisting of
• L3 is selected from the group consisting of a bond, C1-C4 alkyl, and NH;
• each of RE1, RE2, and RE3 is independently selected from the group consisting of H, halo, —CN, and C1-C6 alkyl;
• a is 1 or 2;
• and
• each z is independently 0, 1, or 2.