title: Design, synthesis and antitumor activity of 4-aminoquinazoline derivatives targeting VEGFR-2 tyrosine kinase.
abstract: We report herein the design and synthesis of novel 4-aminoquinazoline derivatives based on the inhibitors of VEGFR-2 tyrosine kinases. The VEGFR-2 inhibitory activities of these newly synthesized compounds were also evaluated and compared with that of ZD6474. We found that most of target compounds had good inhibitory potency. In particular, compounds 1h, 1n and 1o were found to be 6, 2 and 2-fold more potent than the positive control ZD6474. The leading compound 1h also showed an in vivo activity against HepG2 human tumor xenograft model in BALB/c-nu mice.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Li-da
authors.initials: LD
authors.lastname: Tang
authors.forename: Yi-Liang
authors.initials: YL
authors.lastname: Li
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Song
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Ji
authors.forename: Mu-Sen
authors.initials: MS
authors.lastname: Lin
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C573775:4-aminoquinazoline; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010880:Piperidines; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2; C452423:vandetanib