一种 Buchwald-Hartwig 方案，可实现 Cereblon E3 连接酶 PROTAC 的快速连接子探索*。
A Buchwald-Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs*.
机构信息
Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK.
Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Macclesfield Campus, Etherow Building, Silk Road Industrial Estate, Macclesfield, SK10 2NA, UK.
出版信息
Chemistry. 2020 Dec 15;26(70):16818-16823. doi: 10.1002/chem.202003137. Epub 2020 Nov 3.
A palladium-catalysed Buchwald-Hartwig amination for lenalidomide-derived aryl bromides was optimised using high throughput experimentation (HTE). The substrate scope of the optimised conditions was evaluated for a range of alkyl- and aryl- amines and functionalised aryl bromides. The methodology allows access to new cereblon-based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields.
钯催化的 Buchwald-Hartwig 胺化反应用于来那度胺衍生的芳基溴化物，通过高通量实验（HTE）进行了优化。优化条件的底物范围评估了一系列烷基和芳基胺以及功能化芳基溴化物。该方法可用于新的基于 cereblon 的双功能蛋白水解靶向嵌合体，具有减少的步骤数和提高的产率。
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