Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors.

ABSTRACT

A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/ß kinase with IC50 values of 1.5 µM and 3 µM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3ß. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/ß enzymes with potential therapeutic application in Alzheimer's disease.