title: Discovery of new 4-alkoxyquinazoline-based derivatives as potent VEGFR2 inhibitors.
abstract: VEGFR2 has been proved to play a major role in the regulation of tumor angiogenesis. Twenty-one 4-alkoxyquinazoline-based derivatives have been designed and synthesized as vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors, and their biological activities were evaluated. Among these compounds, compound 3h exhibited the most potent inhibitory activities against VEGFR2 tyrosine kinase and cell proliferation, with the IC50 values of 2.89 nm (for VEGFR2) and 0.25 μm (for MCF-7), which were comparable with the control compound. Docking simulation was performed to position compound 3h into the 4ASE active site, and the result showed that compound 3h could bind well at the 4ASE active site.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: She-Feng
authors.initials: SF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: 4-alkoxyquinazoline-based derivatives; VEGFR2 inhibitors; molecular docking