The synthesis of 1-oxa-9-azaspiro[5.5]undecane derivatives and optimization of antituberculosis activity thereof

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-08-21 DOI:10.1007/s10593-024-03328-w

Kristina Yu. Komarova, Alexey Yu. Lukin, Lyubov V. Vinogradova, Maxim E. Zhuravlev, Marine Z. Dogonadze, Tatiana I. Vinogradova, Maxim A. Gureev, Mikhail V. Chudinov, Dmitry V. Dar’in

引用次数: 0

Abstract

The aim of this work was to synthesize and study the antituberculosis activity of spirocyclic inhibitors of the MmpL3 protein of M. tu- berculosis containing the 1-oxa-9-azaspiro[5.5]undecane scaffold. Optimization of the initial structure was performed with consideration of the results of molecular docking. The resulting compounds, characterized by the chemical diversity of the peripheral fragment, showed high activity against the antibiotic-sensitive strain H37Rv and some multiresistant strains of M. tuberculosis, exceeding the activity of the comparator drug.

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1-oxa-9-azaspiro[5.5]undecane 衍生物的合成及其抗结核活性的优化

这项工作的目的是合成和研究含有 1-oxa-9-azaspiro[5.5]undecane 支架的结核杆菌 MmpL3 蛋白的螺环抑制剂的抗结核活性。考虑到分子对接的结果，对初始结构进行了优化。由此产生的化合物以外围片段的化学多样性为特征，对抗生素敏感菌株 H37Rv 和一些结核杆菌多重耐药菌株表现出较高的活性，超过了对比药物的活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.