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Efficient Synthesis of Benzothiazinone Analogues with Activity against Intracellular Mycobacterium tuberculosis
Author(s) -
Richter Adrian,
Narula Gagandeep,
Rudolph Ines,
Seidel Rüdiger W.,
Wagner Christoph,
AvGay Yossef,
Imming Peter
Publication year - 2022
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100733
Subject(s) - antimycobacterial , quinazolinone , mycobacterium tuberculosis , chemistry , combinatorial chemistry , thiourea , broth microdilution , resazurin , stereochemistry , in vitro , tuberculosis , biochemistry , minimum inhibitory concentration , organic chemistry , medicine , pathology
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.