RAS INHIBITORS MACROLYTICS

Abstract

Macrocyclic compounds, pharmaceutical compositions, and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in cancer treatment, are described. This is a compound of Formula I' where A is an optionally substituted 3- to 6-membered cycloalkylene, optionally substituted 3- to 10-membered heterocycloalkylene, among others; L is a linkage or -CH(R20)-N(R21)-C(O)-; W is an optionally substituted 3- to 10-membered heterocycloalkyl or optionally substituted 3- to 10-membered cycloalkyl; X4 is CH2 or NH; R1 is H, C1-C6 alkyl, among others; R2 is H, optionally substituted C1-C6 alkyl, among others; R3 is H, optionally substituted C1-C6 alkyl, among others; R4, R5, R6, R7, R5a, R6a and R7a are each independently H, halo or C1-C6 alkyl, among others; R10 is H, -OR11 or -NR12R13; R11, R12 and R13 are each independently optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, among others.