含腈类药物：作用靶点、作用机制及其构效关系研究
Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies.
作者信息
Wang Xi, Wang Yuanxun, Li Xuemin, Yu Zhenyang, Song Chun, Du Yunfei
机构信息
School of Pharmaceutical Science and Technology, Tianjin University Tianjin 300072 China
National Institution of Biological Sciences, Beijing No. 7 Science Park Road, Zhongguancun Life Science Park Beijing 102206 China.
出版信息
RSC Med Chem. 2021 Aug 10;12(10):1650-1671. doi: 10.1039/d1md00131k. eCollection 2021 Oct 20.
Abstract
The nitrile group is an important functional group widely found in both pharmaceutical agents and natural products. More than 30 nitrile-containing pharmaceuticals have been approved by the FDA for the management of a broad range of clinical conditions in the last few decades. Incorporation of a nitrile group into lead compounds has gradually become a promising strategy in rational drug design as it can bring additional benefits including enhanced binding affinity to the target, improved pharmacokinetic profile of parent drugs, and reduced drug resistance. This paper reviews the existing drugs with a nitrile moiety that have been approved or in clinical trials, involving their targets, molecular mechanism of pharmacology and SAR studies, and classifies them into different categories based on their clinical usages.
摘要
腈基是一种重要的官能团，广泛存在于药物制剂和天然产物中。在过去几十年里，超过30种含腈类药物已被美国食品药品监督管理局（FDA）批准用于治疗多种临床病症。在先导化合物中引入腈基已逐渐成为合理药物设计中的一种有前景的策略，因为它可以带来额外的益处，包括增强对靶点的结合亲和力、改善母体药物的药代动力学特性以及降低耐药性。本文综述了已获批准或正在进行临床试验的含腈基现有药物，涉及它们的靶点、药理分子机制和构效关系（SAR）研究，并根据其临床用途将它们分为不同类别。
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