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

  • J Med Chem. 2014 Sep 25;57(18):7577-89. doi: 10.1021/jm500510f.
Hong Jia  1 ,  Guangxiu Dai ,  Jianyang Weng ,  Zhulin Zhang ,  Qing Wang ,  Feng Zhou ,  Longxian Jiao ,  Yumin Cui ,  Yongxin Ren ,  Shiming Fan ,  Jinghong Zhou ,  Weiguo Qing ,  Yi Gu ,  Jian Wang ,  Yang Sai ,  Weiguo Su
Affiliations
  • 1. Hutchison MediPharma Limited , Building 4, 720 Cai Lun Road, Zhangjiang Hi-Tech Park, 201203, Shanghai, China.
PMID: 25148209 DOI: 10.1021/jm500510f
Abstract

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.

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