Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (10): 2648-2656.DOI: 10.6023/cjoc201803041 Previous Articles     Next Articles



张志华a, 陈羽b, 吴红梅a, 崔博c, 熊武林c, 林腾辉c, 林荣南c, 郭宇a   

  1. a 辽宁工业大学化学与环境工程学院 锦州 121001;
    b 沈阳药科大学生命科学与生物制药学院 沈阳 110016;
    c 锦州医科大学药学院 锦州 121001
  • 收稿日期:2018-03-25 修回日期:2018-06-06 发布日期:2018-06-15
  • 通讯作者: 郭宇,
  • 基金资助:


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

Zhang Zhihuaa, Chen Yub, Wu Hongmeia, Cui Boc, Xiong Wulinc, Lin Tenghuic, Lin Rongnanc, Yu Guoa   

  1. 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
  • Received:2018-03-25 Revised:2018-06-06 Published:2018-06-15
  • Contact: 10.6023/cjoc201803041
  • Supported by:

    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).

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.

Key words: thiazole derivative, c-Met inhibitor, synthesis, structure-activity relationship