Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction
Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction
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DOI：
10.1021/acs.orglett.9b01326
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发表时间：
2019-05-17
期刊：
影响因子：
5.2
通讯作者：
Jiang, Biao
中科院分区：
文献类型：
--
作者：
Qiu, Xing;Sun, Ning;Jiang, Biao
开发了与不同卤化物的Lenalidomide的有机碱基促进的化学选择性烷基化，在轻度反应条件下，该方法为高度功能化的Lenalidomide的Protac库提供了一种新颖的方法。与无机碱基相比，发现二培型可以作为触发芳基胺烷基化产物易于产生的有效碱。该文库成功地应用于BET Protac，不仅降解了BET蛋白，而且还有效地抑制了癌细胞的增殖。
An organic base-promoted chemoselective alkylation of lenalidomide with different halides was developed, which offers a novel approach to a highly functionalized lenalidomide-based PROTAC library under mild reaction conditions. DIPEA was found to act as an efficient base to trigger facile generation of arylamine alkylation products compared with inorganic bases. This library was successfully applied to BET PROTAC, which not only degraded BET protein but also effectively inhibited cancer cell proliferation.