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氮杂环在阿尔茨海默病药物发现中的关键作用。

Pivotal role of nitrogen heterocycles in Alzheimer's disease drug discovery.

机构信息

Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH 43614, USA.

Molecular Targeted Therapeutics Laboratory, Levine Cancer Institute/Atrium Health, Charlotte, NC 28204, USA.

出版信息

Drug Discov Today. 2022 Oct;27(10):103322. doi: 10.1016/j.drudis.2022.07.007. Epub 2022 Jul 19.

Abstract

Alzheimer's disease (AD) is a detrimental neurodegenerative disease that progressively worsens with time. Clinical options are limited and only provide symptomatic relief to AD patients. The search for effective anti-AD compounds is ongoing with a few already in Phase III clinical trials, yet to be approved. Heterocycles containing nitrogen are important to biological processes owing to their abundance in nature, their function as subunits of biological molecules and/or macromolecular structures, and their biological activities. The present review discusses previously used strategies, SAR, relevant in vitro and in vivo studies, and success stories of nitrogen-containing heterocyclic compounds in AD drug discovery. Also, we propose strategies for designing and developing novel potent anti-AD small molecules that can be used as treatments for AD.

摘要

阿尔茨海默病(AD)是一种进行性恶化的神经退行性疾病。目前的临床治疗选择有限,只能为 AD 患者提供症状缓解。人们正在寻找有效的抗 AD 化合物,目前已有少数化合物进入 III 期临床试验,但尚未获得批准。含氮杂环由于其在自然界中的丰富度、作为生物分子和/或大分子结构亚单位的功能以及生物活性,对生物过程非常重要。本综述讨论了先前使用的策略、SAR、相关的体外和体内研究以及含氮杂环化合物在 AD 药物发现中的成功案例。此外,我们还提出了设计和开发新型有效抗 AD 小分子的策略,这些小分子可用于 AD 的治疗。

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