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

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 <b>28</b>, which demonstrated favorable pharmacokinetic properties in mice and good antitumor activities in the human glioma xenograft model in athymic nude mice