title: Synthesis and biological evaluation of novel tricyclic oxazine and oxazepine fused quinazolines. Part 2: Gefitinib analogs.
abstract: Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed and synthesized. The in vitro antitumor effect of the title compounds was screened on N87, A431, H1975, BT474 and Calu-3 cell lines. Compared to gefitinib and erlotinib, compounds 1a-1h were found to demonstrate more potent antitumor activities. Several derivatives could counteract EGF-induced phosphorylation of EGFR in cells, and their potency was comparable to the reference compounds. Compounds 1a-1f, 1h were chosen for further evaluation of EGFR and HER2 in vitro kinase inhibitory activity. Compounds 1c-1f, 1h effectively inhibited the in vitro kinase activity of EGFR and HER2 with similar efficacy as gefitinib and erlotinib.
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China. Electronic address: sunmin@ask-pharm.com.
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Zaiwei
authors.initials: Z
authors.lastname: Zong
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Han
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Youguo
authors.initials: Y
authors.lastname: Du
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Huanliang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Feidong
authors.initials: F
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D010766:Phosphorylation; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Antitumor activity; EGFR; HER2; Tricyclic fused quinazolines