Treventis Corporation, Toronto, Ontario M5T 0S8, Canada.
Department of Fundamental Neurobiology, Krembil Research Institute, Toronto, Ontario M5T 0S8, Canada.
J Med Chem. 2021 Feb 25;64(4):1786-1815. doi: 10.1021/acs.jmedchem.0c01901. Epub 2021 Feb 11.
Incorporation of heterocycles into drug molecules can enhance physical properties and biological activity. A variety of heterocyclic groups is available to medicinal chemists, many of which have been reviewed in detail elsewhere. Oxadiazoles are a class of heterocycle containing one oxygen and two nitrogen atoms, available in three isomeric forms. While the 1,2,4- and 1,3,4-oxadiazoles have seen widespread application in medicinal chemistry, 1,2,5-oxadiazoles (furazans) are less common. This Review provides a summary of the application of furazan-containing molecules in medicinal chemistry and drug development programs from analysis of both patent and academic literature. Emphasis is placed on programs that reached clinical or preclinical stages of development. The examples provided herein describe the pharmacology and biological activity of furazan derivatives with comparative data provided where possible for other heterocyclic groups and pharmacophores commonly used in medicinal chemistry.
杂环化合物的引入可以增强药物分子的物理性质和生物活性。药物化学家可以利用多种杂环基团,其中许多在其他地方已经有详细的综述。恶二唑是一种含有一个氧原子和两个氮原子的杂环,有三种异构体形式。虽然 1,2,4-和 1,3,4-恶二唑在药物化学中得到了广泛的应用,但 1,2,5-恶二唑(呋咱)则不太常见。本综述通过分析专利和学术文献,总结了含呋咱分子在药物化学和药物开发计划中的应用。重点介绍了已进入临床或临床前开发阶段的计划。本文提供的实例描述了呋咱衍生物的药理学和生物学活性,并在可能的情况下提供了与其他杂环基团和药物化学中常用的药效团的比较数据。