Macozinone: revised synthesis and crystal structure of a promising new drug for treating drug-sensitive and drug-resistant tuberculosis

Acta Crystallographica. Section C, Structural Chemistry
Gang Zhang, Courtney C Aldrich

Abstract

Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclohexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzothiazin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzothiazin-4-one group.

References

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Citations

Sep 6, 2020·Acta Crystallographica. Section C, Structural Chemistry·Tamira EckhardtPeter Imming
Sep 18, 2020·Acta Crystallographica. Section E, Crystallographic Communications·Tamira EckhardtRüdiger W Seidel
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 17, 2021·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Balungile MadikizelaRüdiger W Seidel
Aug 18, 2021·Expert Opinion on Pharmacotherapy·Ginenus FekaduJoyce H S You

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