Synthesis and Antitumor Activity of Novel 4-(2-Fluorophenoxy)-quinoline Derivatives Bearing the 4-Oxo-1,4-dihydroquinoline-3-carboxamide Moiety

被引：16

作者：

Li, Sai ^{[1
]}

Jiang, Rui ^{[1
]}

Qin, Mingze ^{[1
]}

Liu, Haicheng ^{[1
]}

Zhang, Guangyan ^{[1
]}

Gong, Ping ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Minist Educ, Key Laboratary Original New Drugs Design & Discov, Shenyang 110016, Peoples R China

来源：

ARCHIV DER PHARMAZIE | 2013年 / 346卷 / 07期

关键词：

Antitumor activity; 4-Oxo-1; 4-dihydroquinoline-3-carboxamide moiety; Synthesis; C-MET INHIBITORS; STRUCTURE-BASED DESIGN; KINASE INHIBITORS; DRUG-RESISTANCE; CANCER; POTENT; DISCOVERY; IDENTIFICATION; PROLIFERATION; METASTASIS;

D O I：

10.1002/ardp.201300029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-(2-fluorophenoxy)quinoline derivatives bearing the 4-oxo-1,4-dihydroquinoline-3-carboxamide moiety were designed, synthesized, and evaluated for their in vitro antitumor activity against the H460, HT-29, MKN-45, U87MG, and SMMC-7721 cancer cell lines. Most of the tested compounds showed potent activity and high selectivity toward the HT-29 and MKN-45 cell lines. Furthermore, compounds 21b, 21c, and 21i were further examined for their c-Met kinase activity and exhibited strong efficacy with IC50 values in the single-digit nanomolar range, which was comparable with the positive control foretinib. The most promising compound 21c showed excellent cytostatic activity with IC50 values from 0.01 to 0.53 mu M against all tested cell lines, thus being 1.7-2.2 times more active than foretinib.

引用

页码：521 / 533

页数：13

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