Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives

Bioorganic & Medicinal Chemistry Letters
Cui-Ting PengLuo-Ting Yu

Abstract

Tuberculosis (TB) remains a major human health problem. New therapeutic antitubercular agents are urgent needed to control the global tuberculosis pandemic. We synthesized a new series of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives and evaluated their anti-mycobacterial activities against Mycobacterium tuberculosis H37Ra as well as their druggabilities. The results showed that most of these derivatives, especially the compounds with simple alkyl side chains, exhibited good antitubercular activities and favorable aqueous solubilities with no obvious cytotoxicity. It suggested that the 4-carbonyl piperazine substituents in benzothiazinone scaffold were well tolerated, in which the compound 8h, with an antitubercular activity of MIC 0.008 μM, exhibited an excellent aqueous solubility of 104 μg/mL, which was 100-fold better than the potent DprE1 inhibitor Comp.1 (BTZ038), also more soluble than PBTZ169.

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Citations

Aug 28, 2015·European Journal of Medicinal Chemistry·Mohammad ShaquiquzzamanMohammad Mumtaz Alam
Jun 10, 2017·Medicinal Research Reviews·Vajinder KumarRahul Jain
Mar 6, 2019·Current Topics in Medicinal Chemistry·Marcus Vinicius Nora de Souza, Thais Cristina Mendonça Nogueira
Sep 24, 2015·Acta Crystallographica. Section E, Crystallographic Communications·Monirah A Al-AlshaikhSantiago Garcia-Granda
Nov 30, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Gabriele A BerwaldtWilson Cunico
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Nov 17, 2020·European Journal of Medicinal Chemistry·Pankaj S GiraseRajshekhar Karpoormath
Jan 20, 2021·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Gang ZhangCourtney C Aldrich
Feb 23, 2021·Acta Crystallographica. Section E, Crystallographic Communications·Adrian RichterRüdiger W Seidel
Jun 1, 2018·Journal of Medicinal Chemistry·Rupesh V ChikhaleMange Ram Yadav

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