Design, synthesis and biological activity of N-(amino)piperazine-containing benzothiazinones against Mycobacterium tuberculosis

Eur J Med Chem. 2021 Mar 28;218:113398. doi: 10.1016/j.ejmech.2021.113398. Online ahead of print.ABSTRACTA series of novel benzothiazinone derivatives containing a N-(amino)piperazine moiety, based on the structure of WAP-1902 discovered in our lab, were designed and synthesized as new anti-TB agents. Many of the compounds exhibited excellent in vitro activity against both drug-sensitive MTB strain H37Rv and multidrug-resistant clinical isolates (MIC: < 0.016 μg/mL), and good safety index (CC50: >64 μg/mL). Especially compound 1o displayed low hERG cardiac toxicity and acceptable oral pharmacokinetic profiles, indicating its promising potential to be a lead compound for future antitubercular drug discovery.PMID:33823392 | DOI:10.1016/j.ejmech.2021.113398
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research