title: Synthesis and biological evaluation of novel tricyclic oxazine and oxazepine fused quinazolines. Part 1: erlotinib 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 erlotinib and gefitinib, 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-1h were chosen for further evaluation of EGFR and HER2 in vitro kinase inhibitory activity. Compounds 1b-1f, 1h effectively inhibited the in vitro kinase activity of EGFR and HER2 with similar efficacy as erlotinib and gefitinib.
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: 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
authors.affiliation: Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, PR China.
authors.forename: Lingsheng
authors.initials: L
authors.lastname: Kong
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
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003500:Cyclization; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010077:Oxazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010770:Phosphotransferases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D010077:Oxazepines; D010078:Oxazines; D010770:Phosphotransferases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: Antitumor activity; EGFR; HER2; Tricyclic fused quinazolines