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苯二氮䓬类化合物的合成与药物化学研究进展。

Recent advances in synthesis and medicinal chemistry of benzodiazepines.

机构信息

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, G.T. Road, Ghal Kalan, Moga 142001, Punjab, India.

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, G.T. Road, Ghal Kalan, Moga 142001, Punjab, India.

出版信息

Bioorg Chem. 2020 Apr;97:103668. doi: 10.1016/j.bioorg.2020.103668. Epub 2020 Feb 17.

Abstract

Benzodiazepines (BZDs) represent a diverse class of bicyclic heterocyclic molecules. In the last few years, benzodiazepines have emerged as potential therapeutic agents. As a result, several mild, efficient and high yielding protocols have been developed that offer access to various functionalized benzodiazepines (BZDs). They are known to possess a wide array of biological activities such as anxiolytic, anticancer, anticonvulsant, antipsychotics, muscle relaxant, anti-tuberculosis, and antimicrobial activities. The fascinating spectrum of biological activities exhibited by BZDs in various fields has prompted the medicinal chemist to design and discover novel benzodiazepine-based analogs as potential therapeutic candidates with the desired biological profile. In this review, an attempt has been made by to summarize (1) Recent advances in the synthetic chemistry of benzodiazepines which enable their synthesis with desired substitution pattern; (2) Medicinal chemistry of BZDs as therapeutic candidates with promising biological profile including insight of mechanistic studies; (3) The correlation of biological data with the structure i.e. structure-activity relationship studies were also included to provide an insight into the rational design of more active agents.

摘要

苯二氮䓬类(BZDs)是一类具有多样结构的双环杂环分子。近年来,苯二氮䓬类已成为具有潜在治疗作用的药物。因此,已经开发出了几种温和、高效和高产的方法,可用于获得各种功能化的苯二氮䓬类(BZDs)。它们具有广泛的生物活性,如抗焦虑、抗癌、抗惊厥、抗精神病、肌肉松弛、抗结核和抗菌活性。BZDs 在各个领域表现出的引人注目的生物活性促使药物化学家设计和发现新型苯二氮䓬类类似物作为具有所需生物学特征的潜在治疗候选物。在这篇综述中,尝试总结了(1)苯二氮䓬类合成化学的最新进展,使它们能够按照所需的取代模式进行合成;(2)BZDs 作为治疗候选物的药物化学,具有有前途的生物学特征,包括对机制研究的深入了解;(3)还包括了生物数据与结构的相关性,即构效关系研究,以深入了解更有效的药物的合理设计。

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