Synthesis, activity and docking studies of phenylpyrimidine-carboxamide Sorafenib derivatives
Synthesis, activity and docking studies of phenylpyrimidine-carboxamide Sorafenib derivatives
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苯基嘧啶甲酰胺索拉非尼衍生物的合成、活性及对接研究
DOI：
10.1016/j.bmc.2016.09.021
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发表时间：
2016
影响因子：
3.5
通讯作者：
Zheng Pengwu
中科院分区：
文献类型：
--
作者：
Wang Wenhui;Wu Chunjiang;Wang Jianqiang;Luo Rong;Wang Caolin;Liu Xiaobo;Li Jiqing;Zhu Wufu;Zheng Pengwu
Two series of Sorafenib derivatives bearing phenylpyrimidine–carboxamide moiety (16a–gand17a–p) were designed, synthesized and evaluated for the IC50values against three cancer cell lines (A549, MCF-7 and PC-3). Two selected compounds (17fand17n) were further evaluated for the activity against VEGFR2/KDR kinase. More than half of the synthesized compounds showed moderate to excellent activity against three cancer cell lines. Compound17fshowed equal activity to Sorafenib against MCF-7 cell line, with the IC50values of 6.35 ± 0.43 μM. Meanwhile, compound17nrevealed more active than Sorafenib against A549 cell line, with the IC50values of 3.39 ± 0.37 μM. Structure–activity relationships (SARs) and docking studies indicated that the second series (17a–p) showed more active than the first series (16a–g). What’s more, the introduction of fluoro atom to the phenoxy part played no significant impact on activity. In addition, the presence of electron-donating on aryl group was benefit for the activity.
