Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development

基于邻苯二甲酰亚胺的 Cereblon 配体的实际合成,以实现 PROTAC 开发

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作者:Jasmin Lohbeck, Aubry K Miller

Abstract

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.

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