Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (6): 1414-1421.DOI: 10.6023/cjoc201802005 Previous Articles     Next Articles



管道坤, 孙少峰, 陈静, 何作鹏, 孔祥凯, 王宁宁, 姚建文, 王洪波   

  1. 烟台大学分子药理和药物评价教育部重点实验室 烟台 264005
  • 收稿日期:2018-02-02 修回日期:2018-03-22 发布日期:2018-04-13
  • 通讯作者: 姚建文,;王洪波,;
  • 基金资助:


Synthesis and Evaluation of Antitumor Activity of Sorafenib Derivatives Possessing Diphenylamine and Thiourea Structures

Guan Daokun, Sun Shaofeng, Chen Jing, He Zuopeng, Kong Xiangkai, Wang Ningning, Yao Jianwen, Wang Hongbo   

  1. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai 264005
  • Received:2018-02-02 Revised:2018-03-22 Published:2018-04-13
  • Contact: 10.6023/cjoc201802005;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81728020), the Key Research Project of Shandong Province (No. 2017GSF18177), and the Key Technology Development Plan of Yantai City (No. 2017ZH075).

17 novel sorafenib derivatives possessing diphenylamine and thiourea structures were designed and synthesized using 2-picolinic acid and substituted anilines as raw materials. The structures of the target compounds were all characterized by NMR and HRMS. In addition, the in vitro antiproliferation activity of the target compounds was studied in human colon cancer cell HCT116, human breast cancer cell line MDA-MB-231, human prostate cancer cell line PC-3 and mouse melanoma cell line B16BL6. The results showed that 1-(4-chloro-3-trifluoromethylphenyl)-3-(4-(2-(isopropylcarbamoyl)pyridine-4-amino)phenyl)thiourea (9g) had better inhibitory activity against four cell lines than the positive drug sorafenib, and 1-(3-trifluoromethyl-4-chlorophenyl)-3-{4-[2-(methylcarbamoyl)pyridine-4-amino]phenyl}thiourea (9b) and 1-(3-trifluoro-methyl-4-fluorophenyl)-3-{4-[2-(isopropylcarbamoyl)pyridine-4-amino]phenyl}thiourea (9j) had better inhibitory activity against MDA-MB-231, PC-3 and B16BL6 cell lines. The molecular docking of the active small molecule 9j was further studied, and its binding mode with the active site of the 3-D crystal structure (5HI2) of B-Raf receptor was discussed, which provided a useful reference for the design and synthesis of novel sorafenib derivatives in the future.

Key words: B-Raf, molecular docking, an-titumor activity, diphenylamine and thiourea, sorafenib derivatives