title: Design and synthesis of 4,6-substituted-(diaphenylamino)quinazolines as potent EGFR inhibitors with antitumor activity.
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)=0.28μM for Hep G2, IC(50)=0.59μM for A16-F10 and IC(50)=0.87μM 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.
authors: College of Pharmaceutical Science, Soochow University, Suzhou 215123, PR China. huanqiuli@suda.edu.cn
authors: Huan-Qiu
authors: HQ
authors: Li
authors: Dong-Dong
authors: DD
authors: Li
authors: Xiang
authors: X
authors: Lu
authors: Yun-Yun
authors: YY
authors: Xu
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008968:Molecular Conformation; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C571775:4-((4-(3-bromophenylamino)quinazolin-6-ylamino)methyl)phenol; D000970:Antineoplastic Agents; D010636:Phenols; D011799:Quinazolines; D066246:ErbB Receptors