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Title: Efficient synthesis of benzothiazinone analogues with activity against intracellular mycobacterium tuberculosis
Author(s): Richter, AdrianLook up in the Integrated Authority File of the German National Library
Narula, Gagandeep
Rudolph, Ines
Seidel, Rüdiger W.Look up in the Integrated Authority File of the German National Library
Wagner, Christoph
Av-Gay, Yossef
Imming, PeterLook up in the Integrated Authority File of the German National Library
Issue Date: 2021
Type: Article
Language: English
Abstract: We report the synthesis of antitubercular 8-nitrobenzothiazinones and their antimycobacterial characterization. A synthesis using thiourea intermediates was established, and 35 analogues were prepared. Their antimycobacterial potential was investigated against Mycobacterium tuberculosis: minimal inhibitory concentrations (MICs) of all derivatives were determined in broth and in a macrophage infection model. Compounds with MICs of <50 nM could be described and characterized. 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.
Open Access: Open access publication
License: (CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0(CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0
Sponsor/Funder: Publikationsfonds MLU
Journal Title: ChemMedChem
Publisher: Wiley-VCH
Publisher Place: Weinheim [u.a.]
Original Publication: 10.1002/cmdc.202100733
Appears in Collections:Open Access Publikationen der MLU