Hales Liam Thomas, Thompson Philip Evan
Medicinal Chemistry, Monash Institute of Pharmaceutical Science, Monash University, Parkville, VIC, Australia.
Chemistry. 2023 Oct 9;29(56):e202301975. doi: 10.1002/chem.202301975. Epub 2023 Sep 7.
Developing straightforward but flexible approaches to PROTAC synthesis that can incorporate the structural elements of emerging designs can improve the quality and efficiency of PROTAC development. Solid-phase approaches could offer many advantages over conventional PROTAC synthesis if diverse chemistries and topographies can be incorporated. We have exploited the backbone-amide-linked (BAL) resin to employ an array of solid-phase organic reactions, providing access to VHL- and IAP-targeting degraders using the BRD4-targeting JQ1 conjugates as examples.
开发直接但灵活的PROTAC合成方法，使其能够纳入新出现设计的结构元素，可提高PROTAC开发的质量和效率。如果能够纳入多种化学性质和拓扑结构，固相方法可能比传统的PROTAC合成具有许多优势。我们利用主链酰胺连接（BAL）树脂进行一系列固相有机反应，以靶向BRD4的JQ1缀合物为例，获得了靶向VHL和IAP的降解剂。
