title: Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors.
abstract: Crown ether fused anilinoquinazoline analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities in an in vitro EGFR kinase assay and an EGFR-mediated intracellular tyrosine phosphorylation assay. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation of these fused quinazoline compounds is reported.
authors.affiliation: Zhejiang Betapharma, 589 Hongfong Rd., YuhangDistrict, Zhejiang 311100, PR China. shaojing.hu@betapharma.com.cn
authors.forename: Shaojing
authors.initials: S
authors.lastname: Hu
authors.forename: Guojian
authors.initials: G
authors.lastname: Xie
authors.forename: Don X
authors.initials: DX
authors.lastname: Zhang
authors.forename: Charles
authors.initials: C
authors.lastname: Davis
authors.forename: Wei
authors.initials: W
authors.lastname: Long
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Hu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xinshan
authors.initials: X
authors.lastname: Kang
authors.forename: Fenlai
authors.initials: F
authors.lastname: Tan
authors.forename: Lieming
authors.initials: L
authors.lastname: Ding
authors.forename: Yinxiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D043844:Crown Ethers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D043844:Crown Ethers; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors