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

被引：1

作者：

Sun, Chang'an

Fang, Lei ^{[1
]}

Gou, Shaohua ^{[1
]}

机构：

[1] Southeast Univ, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing 211189, Peoples R China

来源：

CHINESE JOURNAL OF ORGANIC CHEMISTRY | 2020年 / 40卷 / 01期

关键词：

selective FGFR4 inhibitor; analogues of FRF401; structure-activity relationship; hepatocellular carcinoma; HEPATOCELLULAR-CARCINOMA;

D O I：

10.6023/cjoc201904073

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：84 / 94

页数：11

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