BCL-XL HETEROBIFUNCTIONAL TETRAHYDROISOQUINOLINE DEGRADERS

Abstract

The present invention relates to compounds of formula (I-a1) or (I-a2), or a pharmaceutically acceptable salt thereof, wherein: Z1 is CH or N; R1 is -C(O)OH, among others; R2 is -CH3 or -CF3; LA4a is selected from the group consisting of a C4-8 cycloalkylene and a 4-10 member nitrogen-containing heterocyclylene, among others; LA4b is a 4-10 member nitrogen-containing heterocyclylene, among others; each LA1b is an independently selected LA1; each LA1 is -CH2-, among others; a1b is 2, 3, or 4. On ring C, RYa is -H, among others; RYb is independently selected from the group consisting of Ra and Rb; c1 is 0, 1, or 2; and yy represents the attachment point to LA4b; Ra is independently halo, -CN, among others; Rb is -Rb1, among others; and each Rb1 is independently a C3-6 cycloalkyl or a 4-8 membered heterocyclyl, among others.Furthermore, the invention relates to a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof. The compound or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition, is used to treat cancer, including breast cancer, lung cancer, colorectal cancer, hematological cancer, and other types of cancer.