RAS INHIBITORS

Abstract

Macrocyclic compounds, pharmaceutical compositions, and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in cancer treatment, are presented. A compound, or a pharmaceutically acceptable salt thereof, having the structure of Formula I, wherein: Q is an optionally substituted 7- to 12-membered bicyclic arylene, an optionally substituted 7- to 12-membered bicyclic heteroarylene, or an optionally substituted 7- to 12-membered bicyclic heterocyclylene; X is a linker, an optionally substituted linear-chain C1-C3 alkylene with 1 to 3 substituents independently selected from fluoro, -CN, among others; Y is -O-, -NH-, or -N(C1-C3 alkyl)-; R3 is optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, among others; W is (a) or (b); A is optionally substituted C2-C4 alkylene, optionally substituted C1-C4 heteroalkylene, among others; L is formula VIIa or VIIb;R10 is H, halogen, optionally substituted C1-C3 alkyl or optionally substituted C1-C3 heteroalkyl; R7 is H, halogen or optionally substituted C1-C3 alkyl; R8 is H, halogen, -OH, among others; R6 is H or -CH3.;