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
Mar 1, 1969·Journal of Medicinal Chemistry·D E WelchB A Burton
Nov 8, 2003·Acta Crystallographica. Section C, Crystal Structure Communications·T NarasimhamurthyRavindranath S Rathore
Mar 21, 2009·Science·Vadim MakarovStewart T Cole
Sep 11, 2010·Journal of the American Chemical Society·Claudia TrefzerKai Johnsson
Feb 25, 2011·Journal of Medicinal Chemistry·Minoru Ishikawa, Yuichi Hashimoto
Dec 23, 2011·Journal of the American Chemical Society·Claudia TrefzerKai Johnsson
Aug 25, 2012·Journal of Medicinal Chemistry·Tomislav KaroliMatthew A Cooper
Sep 8, 2012·Science Translational Medicine·João NeresClaudia Binda
Nov 12, 2013·Nature Chemical Biology·Rafael M CouñagoChristopher A McDevitt
Feb 7, 2014·EMBO Molecular Medicine·Vadim MakarovStewart T Cole
Dec 30, 2014·Acta Crystallographica. Section A, Foundations and Advances·George M Sheldrick
Jan 9, 2015·Acta Crystallographica. Section C, Structural Chemistry·George M Sheldrick
Aug 22, 2015·Organic Letters·Changming XuSanzhong Luo
Apr 7, 2016·Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials·Colin R GroomSuzanna C Ward
Sep 7, 2018·Journal of Medicinal Chemistry·Sébastien L DegorceJames S Scott
Dec 6, 2018·Tuberculosis·Krishnamohan AtmakuriHazel M Dockrell
Mar 21, 2019·ACS Medicinal Chemistry Letters·Gang ZhangCourtney C Aldrich
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