Discovery of novel 2-substituted-4-phenoxypyridine derivatives as potential antitumor agents

被引：6

作者：

Duan, Yongli ^{[1
]}

Xu, Shan ^{[1
]}

Xiong, Hehua ^{[1
]}

Wang, Linxiao ^{[1
]}

Zhao, Bingbing ^{[1
]}

Wang, Ping ^{[1
]}

Wang, Caolin ^{[1
]}

Peng, Yiqing ^{[1
]}

Cai, Shifan ^{[1
]}

Luo, Rong ^{[2
]}

Zheng, Pengwu ^{[1
]}

Tang, Qidong ^{[1
]}

机构：

[1] Jiangxi Sci & Technol Normal Univ, Sch Pharm, Jiangxi Prov Key Lab Drug Design & Evaluat, Nanchang 330013, Jiangxi, Peoples R China

[2] Jiangxi Prov Inst Mat Medica, Nanchang 330000, Jiangxi, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Synthesis; 4-Phenoxypyridine derivatives; 1,8-Naphthyridinone; Antiproliferative activity; c-Met; Flt-3; C-MET INHIBITORS; 6,7-DISUBSTITUTED-4-PHENOXYQUINOLINE DERIVATIVES; CANCER; DESIGN; ANGIOGENESIS; METASTASIS; VEGFR-2; BEARING; MOIETY; KINASE;

D O I：

10.1016/j.bmcl.2017.12.063

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-alpha, PDGFR-beta, c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC50 values of 2.18/2.61 nM. Structure-activity relationship studies indicated that n-Pr served as R-1 group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R-2 = 4-F) was benefited to the potency. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：254 / 259

页数：6

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