Citation: Sun Chang'an, Fang Lei, Gou Shaohua. Discovery of a Novel FGFR4 Selective Inhibitor via Structure-Activity Relationship Studies of FGF401[J]. Chinese Journal of Organic Chemistry, ;2020, 40(1): 84-94. doi: 10.6023/cjoc201904073 shu

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

Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189

Corresponding author: Fang Lei, lei.fang@seu.edu.cn Gou Shaohua, sgou@seu.edu.cn
Received Date: 29 April 2019
Revised Date: 31 August 2019
Available Online: 18 January 2019
Fund Project: the National Science and Technology Major Foundation of China 2013ZX09402102-001-006Project 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)the Priority Academic Program Development of Jiangsu Higher Education Institutions 1107047002

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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.
- selective FGFR4 inhibitor,
- analogues of FRF401,
- structure-activity relationship,
- hepatocellular carcinoma
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