Design and synthesis of 4,6-substituted-(diaphenylamino)quinazolines as potent EGFR inhibitors with antitumor activity.

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Li HQ, Li DD, Lu X, Xu YY, Zhu HL

Design and synthesis of 4,6-substituted-(diaphenylamino)quinazolines as potent EGFR inhibitors with antitumor activity.

Bioorg Med Chem. 2012 Jan 1;20(1):317-23. doi: 10.1016/j.bmc.2011.10.085. Epub 2011 Nov 6.

PubMed ID

22112541 [ View in PubMed

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Abstract

A type of novel 4,6-substituted-(diaphenylamino)quinazolines, which designed based on the 4-(phenylamino)quinazoline moiety, have been discovered as potential EGFR inhibitors. These compounds displayed good antiproliferative activity and EGFR-TK inhibitory activity. Especially, 4-((4-(3-bromophenylamino)quinazolin-6-ylamino)methyl)phenol (5b), showed the most potent inhibitory activity (IC(50)=0.28muM for Hep G2, IC(50)=0.59muM for A16-F10 and IC(50)=0.87muM for EGFR) and effectively induces apoptosis in a dose-dependent manner in the Hep G2 cell line. Molecular docking of 5b into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Erlotinib	Epidermal growth factor receptor	IC 50 (nM)	30	N/A	N/A	Details