Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development
Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development
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DOI：
10.1016/j.bmcl.2016.09.048
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发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Miller, Aubry K.
中科院分区：
文献类型：
--
作者：
Lohbeck, Jasmin;Miller, Aubry K.
在未来几年，利用小分子来调节特定蛋白质的细胞水平将成为一项强大的技术。利用这种方法的任何项目成功的关键将是能够合成候选小分子文库以在细胞系统中进行测试。在此，我们描述了一种基于邻苯二胺的支架的实际合成，该支架可以很容易地多样化以制造cereblon靶向PROTACs。我们通过合成四种胺的“PROTAC工具箱”来证明这种方法的有效性，这些胺可以直接偶联到抑制剂上。(C) 2016 Elsevier Ltd.版权所有。
The use of small molecules to regulate cellular levels of specific proteins is poised to become a powerful technique in the coming years. Critical to the success of any project utilizing such an approach will be the ability to synthesize libraries of candidate small molecules for testing in cellular systems. Herein, we describe a practical synthesis of a phthalimide-based scaffold, which can be easily diversified to make Cereblon-targeting PROTACs. We demonstrate the effectiveness of this approach by synthesizing a 'PROTAC toolbox' of four amines which can be coupled to inhibitors in a straightforward manner. (C) 2016 Elsevier Ltd. All rights reserved.