Design and Characterization of 1,3-Dihydro-2H-benzo[d]azepin-2-ones as Rule-of-5 Compliant Bivalent BET Inhibitors,ACS Medicinal Chemistry Letters

当前位置： X-MOL 学术 › ACS Med. Chem. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Design and Characterization of 1,3-Dihydro-2H-benzo[d]azepin-2-ones as Rule-of-5 Compliant Bivalent BET Inhibitors
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2023-08-14 , DOI: 10.1021/acsmedchemlett.3c00242
Paul Bamborough ₁ , Chun-Wa Chung ₁ , Nicole C Goodwin ₂ , Darren J Mitchell ₁ , Christopher E Neipp ₂ , Alex Phillipou ₁ , Alex Preston ₁ , Rab K Prinjha ₁ , Peter E Soden ₁ , Robert J Watson ₁ , Emmanuel H Demont ₁

Affiliation

The 1,3-dihydro-2H-benzo[d]azepin-2-ones are potent and ligand-efficient pan-BET bromodomain inhibitors. Here we describe the extension of this template to exploit a bivalent mode of action, binding simultaneously to both bromodomains. Initially the linker length and attachment vectors compatible with bivalent binding were explored, leading to the discovery of exceptionally potent bivalent BET inhibitors within druglike rule-of-5 space.

中文翻译：

1,3-二氢-2H-苯并[d]氮杂-2-酮类化合物作为符合 5 规则的二价 BET 抑制剂的设计和表征

1,3-二氢-2 H-苯并[ d ]azepin-2-酮是有效且配体有效的泛 BET 溴结构域抑制剂。在这里，我们描述了该模板的扩展，以利用二价作用模式，同时结合两个溴结构域。最初探索了与二价结合相容的接头长度和附着载体，从而在药物样五规则空间内发现了异常有效的二价 BET 抑制剂。

更新日期：2023-08-14

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南