Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core.
Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core.
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发现一种具有 3-((2,3,4,5-四氢-1H-苯并[d]氮杂-7-基)氨基)吡嗪核心的有效酪氨酸激酶 AXL 抑制剂。
DOI：
10.1016/j.bmcl.2019.01.018
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发表时间：
2019
影响因子：
2.7
通讯作者：
Zilan Song
中科院分区：
文献类型：
--
作者：
Yueliang Wang;L. Xing;Yin;Jiqing Ye;Yang Dai;Wangting Gu;Jing Ai;Zilan Song
从最近上市的FLT3/AXL多靶点抑制剂Gilteritinib(5)开始，我们进行了侧链环闭合药物化学方法，在生化和细胞抗增殖实验中鉴定了化合物15cas，其ic50值分别为1.2和0.3 nM。与对照化合物相比，我们新发现的AXL抑制剂在两种检测中都更有效。
Starting from the recently launched FLT3/AXL multi-targeted inhibitor Gilteritinib (5), we conducted a side-chain ring closure medicinal chemistry approach leading to the identification of compound15cas a highly potent AXL inhibitor in the biochemical and cellular anti-proliferative assays, with IC50values of 1.2 and 0.3 nM, respectively. Compared with the reference compound5, our new discovered AXL inhibitor15cis more potent in both assays.