Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (1): 84-94.DOI: 10.6023/cjoc201904073 Previous Articles     Next Articles


孙长安, 房雷, 苟少华   

  1. 东南大学化学化工学院 江苏省生物药物高技术研究重点实验室 南京 211189
  • 收稿日期:2019-04-29 修回日期:2019-08-31 发布日期:2019-09-18
  • 通讯作者: 苟少华, 房雷;
  • 基金资助:

Discovery of a Novel FGFR4 Selective Inhibitor via Structure-Activity Relationship Studies of FGF401

Sun Chang'an, Fang Lei, Gou Shaohua   

  1. Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189
  • Received:2019-04-29 Revised:2019-08-31 Published:2019-09-18
  • Supported by:
    Project supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. 1107047002) and the National Science and Technology Major Foundation of China (No. 2013ZX09402102-001-006).

A set of analogues of FRF401 were designed and synthesized, and their FGFR4 inhibition and antitumor activity as well as the structure-activity relationship (SAR) studies were screened. It was found that N-(5-cyano-4-((2-methoxyethyl)-amino)pyridin-2-yl)-7-formyl-6-((N-methyltetrahydro-2H-pyran-4-carboxamido)methyl)-1,2,3,4-tetrahydro-1,8-naphthyridine-1-carboxamide (8ac) not only showed superior FGFR4 inhibitory activity compared with FGF401 and excellent selectivity in enzymatic and cellular level, but also dramatically inhibited tumor growth and induced tumor regression in hepatocellular carcinoma xenograft model.

Key words: selective FGFR4 inhibitor, analogues of FRF401, structure-activity relationship, hepatocellular carcinoma