Targeting EGFR tyrosine kinase: Design, Synthesis and Biological Evaluation of Novel Quinazolinone Derivatives

In this study, two novel series of EGFR-TKIs containing quinazolinone core were designed and synthesized. Most compounds showed reasonable inhibitory activity against EGFR-TK compared to that of erlotinib, a reversible inhibitor of this enzyme. Compound 8b, 2-((2-Chlorobenzyl)amino)-6-phenoxyquinazolin-4(1H)-one, with an IC50 value of 1.37 nM exhibited the highest potency. Molecular docking study of compound 8b showed that it had the same direction of erlotinib and formed proper hydrogen bonds and hydrophobic interactions with the important amino acid residues of the active site. Based on in silico calculations of ADME properties, our novel compounds have the potential to be orally active agents.
Source: Iranian Journal of Pharmaceutical Research - Category: Drugs & Pharmacology Source Type: research