Apocalypse inducers for cancer, immune and autoimmune diseases

摘要

A formula compound (I),where X is heteroaryl optionally substituted with one, two, three or four R4; Y1 is phenyl or heteroarylene C5-C6 optionally fused with one or two rings selected from C3-C8 cycloalkane, C3-C8 cycloalkene, among others; where Y1 is optionally substituted with one, two, three or four substituents selected from R5, OR5, SR5, among others; L1 is (CR6R7) q, (CR6R7) s, -O- (CR6R7) r, among others; Y2 is C3-C11 branched chain, C3-C7 cycloalkyl, C4-C7 cycloalkenyl, among others. Y2 is optionally substituted with one, two, three, four or five substituents selected from R8, OR8, SR8, among others; Z1 is C (O) OR9, C (O) NR10R11, C (O) R11, among others; R1 is halo,R2 is deuterium, halo, C1-C6 alkyl, among others; R3 is halo, C1-6, alkyl, among others; R4 is CN, NO2, halogen, among others; R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, among others; R6 and R7 are H, R15, OR15, among others; R8 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, among others; R9 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, among others; R10 and R11 are H, C1-C6 alkyl, C2-C6 alkenyl, among others; R15 is C1-C4 alkyl; C2-C4 alkenyl, C2-C4 alkynyl, among others; q is 1, 2, or 3; s, r and m are 0, 1, 2 or 3 where the sum of s and r is 0, 1 or 2; m is 0, 1, 2 or 3; n is a number from 0-6 and p is 0,One or two He also mentioned a pharmaceutical composer These compounds inhibit the activity of Bcl-xL's anti Apocalypse protein and can be used to treat cancer, such as bladder cancer, brain cancer, breast cancer, etc.