Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: Design, synthesis and biological evaluation

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• 作者：Chen Wang ; Hongping Gao ; Jinyun Dong ; Yanmin Zhang ; Ping Su ; Yaling Shi ; Jie Zhang
• 关键词：Angiogenesis ; VEGFR-2 inhibitor ; Biphenyl scaffold ; Urea moiety
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：1 January, 2014
• 年：2014
• 卷：22
• 期：1
• 页码：277-284
• 全文大小：2836 K

文摘

A series of novel biphenyl urea derivates were synthesized and investigated for their potential to inhibit vascular endothelial growth factor receptor-2 (VEGFR-2). In particular, A7, B3 and B4 displayed significant enzymatic inhibitory activities, with IC₅₀ values of 4.06, 4.55 and 5.26 nM. Compound A7 exhibited potent antiproliferative activity on several cell lines. SAR study suggested that the introduction of methyl at ortho-position of the biphenyl urea and tertiary amine moiety could improve VEGFR-2 inhibitory activity and antitumor effects. Molecular docking indicated that the urea moiety formed four hydrogen bonds with DFG residue. These biphenyl ureas could serve as promising lead compounds for further optimization.