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

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-(trifluorometh yl)-4H-1,3-benzo thia zin-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 cyclo hexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzo thia zin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp ²-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzo thia zin-4-one group.