SUBSTITUTED DIHYDROISOQUINOLINONE COMPOUNDS

摘要

This invention relates to compounds of general formula (I);;in which R1, R2, R3, R4, L, X and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

主权项

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from the group consisting of H, F, C1-C4 alkyl, C1-C4 alkoxy, C(O)R5, C3-C8 cycloalkyl, 3-12 membered heterocyclyl and 5-12 membered heteroaryl, where each said C1-C4 alkyl or C1-C4 alkoxy is optionally substituted by one or more R6, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by one or more R7; R2 is H, F or C1-C4 alkyl; L is a bond or a C1-C4 alkylene; R3 is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, OH, CN, C(O)R8, COOR9, NR10R11, OR12, C3-C8 cycloalkyl, 3-12 membered heterocyclyl and 5-12 membered heteroaryl, where each said C1-C4 alkyl or C1-C4 alkoxy is optionally substituted by one or more R6, and each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by one or more R7; R4 is H, halo or C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R6; R5 is C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R14; each R6 is independently OH, F, CN or C1-C4 alkoxy; each R7 is independently C1-C4 alkyl, OH, F, CN, C1-C4 alkoxy, ═O, CHO, C(O)R13, SO2R13 or 3-6 membered heterocyclyl; R8 is C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R14; R9 is H or C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R14; R10 and R11 are independently H or C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R14; R12 is selected from the group consisting of C3-C8 cycloalkyl, 3-12 membered heterocyclyl and 5-12 membered heteroaryl, where each said C3-C8 cycloalkyl, 3-12 membered heterocyclyl or 5-12 membered heteroaryl is optionally substituted by one or more R7; each R13 is independently C1-C4 alkyl, where each said C1-C4 alkyl is optionally substituted by one or more R15; each R14 and R15 is independently OH, F, CN or C1-C4 alkoxy; and X and Z are independently C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy or C1-C4 fluoroalkoxy.