Discovery of novel VEGFR-2 inhibitors. Part II: biphenyl urea incorporated with salicylaldoxime.
Discovery of novel VEGFR-2 inhibitors. Part II: biphenyl urea incorporated with salicylaldoxime.
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DOI：
10.1016/j.ejmech.2014.11.032
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发表时间：
2015-01
影响因子：
6.7
通讯作者：
Hongping Gao;P. Su;Yaling Shi;Xiu‐Min Shen;Yanmin Zhang;Jinyun Dong;Jie Zhang
中科院分区：
文献类型：
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作者：
Hongping Gao;P. Su;Yaling Shi;Xiu‐Min Shen;Yanmin Zhang;Jinyun Dong;Jie Zhang
报道了一系列新型的以肟为铰链结合片段的VEGFR-2抑制剂。采用分子内氢键形成假六元环的策略来模拟平面喹唑啉。在VEGFR-2的铰链区中首次引入了肟基的相互作用。大多数被测试的化合物都显示出中等到高度的VEGFR-2抑制活性。其中，12L、12PAN12表现出显著的酶抑制活性和抗肿瘤细胞增殖活性。分子对接表明，水杨醛肟与铰链区形成了两个氢键。这些联苯基脲类化合物有望成为开发新型抗癌药物的先导化合物。
A series of novel VEGFR-2 inhibitors containing oxime as hinge binding fragment were described. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bond was employed to mimic the planar quinazoline. The oxime group was firstly introduced to interact with hinge region of VEGFR-2. Most of compounds tested showed moderate to high VEGFR-2 inhibitory activity. In particular,12l,12pand12yexhibited significant enzymatic inhibitory activity as well as potent antiproliferative activity against cancer cells. Molecular docking suggested that the salicylaldoxime formed two hydrogen bonds with hinge region. These biphenylureas could serve as promising lead compounds for developing novel anticancer agents.