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高效合成具有抗结核分枝杆菌细胞内活性的苯并噻嗪酮类似物。

Efficient Synthesis of Benzothiazinone Analogues with Activity against Intracellular Mycobacterium tuberculosis.

机构信息

Institut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle, Germany.

Department of Medicine, Division of Infectious Diseases, University of British Columbia, 2503-2350 Health Sciences Mall, Vancouver, V6T 1Z3, BC, Canada.

出版信息

ChemMedChem. 2022 Mar 18;17(6):e202100733. doi: 10.1002/cmdc.202100733. Epub 2021 Dec 23.

DOI:10.1002/cmdc.202100733
PMID:34939744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9303563/
Abstract

8-Nitrobenzothiazinones (BTZs) are a promising class of antimycobacterial agents currently under investigation in clinical trials. Starting from thiourea derivatives, a new synthetic pathway to BTZs was established. It allows the formation of the thiazinone ring system in one synthetic step and is applicable for preparation of a wide variety of BTZ analogues. The synthetic procedure furthermore facilitates the replacement of the sulphur atom in the thiazinone ring system by oxygen or nitrogen to afford the analogous benzoxazinone and quinazolinone systems. 36 BTZ analogues were prepared and tested in luminescence-based assays for in vitro activity against Mycobacterium tuberculosis (Mtb) using the microdilution broth method and a high-throughput macrophage infection assay.

摘要

8-硝基苯并噻嗪酮（BTZs）是一类有前景的抗分枝杆菌药物，目前正在临床试验中进行研究。本研究从硫脲衍生物出发，建立了一条新的 BTZs 合成途径。该途径可以在一步合成中形成噻嗪酮环系统，并且适用于制备各种 BTZ 类似物。此外，该合成方法还可以促进噻嗪酮环系统中的硫原子被氧或氮取代，从而得到类似的苯并恶嗪酮和喹唑啉酮系统。本研究共制备了 36 种 BTZ 类似物，并采用微量稀释肉汤法和高通量巨噬细胞感染测定法，在基于发光的体外抗结核分枝杆菌（Mtb）活性测定实验中对其进行了测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7618/9303563/add140a9bbf0/CMDC-17-0-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7618/9303563/42e2d8c98b81/CMDC-17-0-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7618/9303563/2c8585415815/CMDC-17-0-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7618/9303563/fb2da75ea892/CMDC-17-0-g008.jpg
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