Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (Volitinib) as a Highly Potent and Selective Mesenchymal-Epithelial Transition Factor (c-Met) Inhibitor in Clinical Development for Treatment of Cancer

被引：116

作者：

Jia, Hong ^{[1
]}

Dai, Guangxiu ^{[1
]}

Weng, Jianyang ^{[1
]}

Zhang, Zhulin ^{[1
]}

Wang, Qing ^{[1
]}

Zhou, Feng ^{[1
]}

Jiao, Longxian ^{[1
]}

Cui, Yumin ^{[1
]}

Ren, Yongxin ^{[1
]}

Fan, Shiming ^{[1
]}

Zhou, Jinghong ^{[1
]}

Qing, Weiguo ^{[1
]}

Gu, Yi ^{[1
]}

Wang, Jian ^{[1
]}

Sai, Yang ^{[1
]}

Su, Weiguo ^{[1
]}

机构：

[1] Hutchison MediPharma Ltd, Shanghai 201203, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 18期

关键词：

HEPATOCYTE GROWTH-FACTOR; RECEPTOR; IDENTIFICATION; EXPRESSION; OPTIMIZATION; CANDIDATE;

D O I：

10.1021/jm500510f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

HGF/c-Met signaling has been implicated in human cancers. Herein we describe the invention of a series of novel triazolopyrazine c-Met inhibitors. The structure activity relationship of these compounds was investigated, leading to the identification of compound 28, which demonstrated favorable pharmacokinetic properties in mice and good antitumor activities in the human glioma xenograft model in athymic nude mice.

引用

页码：7577 / 7589

页数：13

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