Citation: Zhang Zhihua, Chen Yu, Wu Hongmei, Cui Bo, Xiong Wulin, Lin Tenghui, Lin Rongnan, Yu Guo. Design, Synthesis, and Biological Evaluation of Novel 2-Amino-4-phenylthiazole Derivatives as c-Met Inhibitors[J]. Chinese Journal of Organic Chemistry, ;2018, 38(10): 2648-2656. doi: 10.6023/cjoc201803041 shu

Design, Synthesis, and Biological Evaluation of Novel 2-Amino-4-phenylthiazole Derivatives as c-Met Inhibitors

Zhang Zhihua ^a ,
Chen Yu ^b ,
Wu Hongmei ^a ,
Cui Bo ^c ,
Xiong Wulin ^c ,
Lin Tenghui ^c ,
Lin Rongnan ^c ,
Yu Guo ^a,,

a.
School of Chemical and Environmental Engineering, Liaoning University of Technology, Jinzhou 121001
b.
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016
c.
College of Pharmacy, Jinzhou Medical University, Jinzhou 121001

Corresponding author: Yu Guo, guoyulnut@163.com
Received Date: 25 March 2018
Revised Date: 6 June 2018
Available Online: 15 October 2018
Fund Project: Project supported by the National Natural Science Foundation for Young Scientists of China (No. 21601075), the Natural Science Foundation of Liaoning Province (No. 2015020249) and the General Research Projects of Liaoning Provincial Department of Education (No. JQL201715410)the National Natural Science Foundation for Young Scientists of China 21601075the Natural Science Foundation of Liaoning Province 2015020249the General Research Projects of Liaoning Provincial Department of Education JQL201715410

Figures(7)

Two series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized based on the structural features of crizotinib. The cell proliferation inhibition efficacy was estimated against A549, HT29, Hela and Karpas299 cell lines. The results revealed that some target compounds exhibited strong or moderate proliferation inhibition efficacy against tumor cells. N-(3-(2-Aminothiazol-4-yl)phenyl)-3-chlorobenzamide (3d) displayed significant activity against HT29 cancer cell with IC₅₀ value of 4.42 μmol/L, and influence of this compound on the expression of related proteins in the MET signaling pathway in HT29 cells was investigated by Western blot. In addition, the preliminary structure-activity relationship (SAR) of the derivatives was rationalized by docking studies.
- thiazole derivative,
- c-Met inhibitor,
- synthesis,
- structure-activity relationship
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