O‐Linked Triazolotriazines: Potent and Selective c‐Met Inhibitors
O‐Linked Triazolotriazines: Potent and Selective c‐Met Inhibitors
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DOI：
10.1002/cmdc.201200145
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发表时间：
2012-07
期刊：
影响因子：
3.4
通讯作者：
Fang Chen;Ying Wang;Jing Ai;Zhengsheng Zhan;Yongcong Lv;Zhongjie Liang;C. Luo;De-sheng Mei;M. Geng;W. Duan
中科院分区：
文献类型：
--
作者：
Fang Chen;Ying Wang;Jing Ai;Zhengsheng Zhan;Yongcong Lv;Zhongjie Liang;C. Luo;De-sheng Mei;M. Geng;W. Duan
HGF/c-Met信号通路介导多种重要的生物学活性，但该通路的失调也与多种人类癌症的预后不良密切相关。c-Met被认为是抗癌药物发现中最有前途的治疗靶点之一。在本文中，我们报告了一系列O-连接的三唑并三嗪的发现，其显示出亚纳摩尔的c-Met活性抑制。在这些新化合物中，6 a在酶和细胞测定中均表现出高c-Met抑制效力，具有很大的选择性。
The HGF/c‐Met signaling pathway mediates a variety of important biological activities, but dysregulation of the pathway is also closely associated with poor prognosis in a wide range of human cancers. c‐Met is considered to be among the most promising therapeutic targets for anticancer drug discovery. Herein we report the discovery of a series of O‐linked triazolotriazines that show sub‐nanomolar inhibition of c‐Met activity. Among these new compounds, 6 a exhibits high c‐Met inhibitory potency in both enzymatic and cellular assays with great selectivity.