SUBSTITUTED ETHYNYL HETEROBICYCLIC COMPOUNDS AS TYROSINE KINASE INHIBITORS

摘要

The present disclosure provides a compound of formula (I) and the use thereof for the therapeutic treatment of human cancers including B-cell lymphoma and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.;

主权项

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is selected from the group consisting of —(CH2)m—, —O(CH2)m—, —NR6(CH2)m— and a bond; and where m is an integer from 1-3; W is CR7 or N; R is a cyclic group selected from the group consisting of unsubstituted or substituted aryl, unsubstituted or substituted bicyclic aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted bicyclicheteroaryl; R1 and R2 are independently selected from the group consisting of H, —COR8, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted C3-C8 cycloheteroalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; or R1 and R2 may combine with an atom or atoms to which they are attached to form unsubstituted or substituted C3-12 cycloalkyl, unsubstituted or substituted 3- to 12-membered heterocyclic, unsubstituted or substituted C6-12 aryl, or unsubstituted or substituted 5- to 12-membered heteroaryl; and R3, R4 and R5 are each independently selected from the group consisting of H, halogen, —CN, —CF3, —OCF3, —OR9, —OCOR10, —CO2R11, —COR12, —CONR13R14, —NR15R16, —NR17COR18, —NR19SO2R20, —SOwR21, —SO2NR22R23, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted C3-C8 cycloheteroalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; and where w is an integer from 0-2; wherein R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22 and R23 are each independently selected from the group consisting of unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted C3-C8 cycloheteroalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; or R13 and R14, R15 and R16, or R22 and R23 may combine with an atom or atoms to which they are attached to form unsubstituted or substituted C3-12 cycloalkyl, unsubstituted or substituted 3- to 12-membered heterocyclic, unsubstituted or substituted C6-12 aryl, or unsubstituted or substituted 5- to 12-membered heteroaryl.