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

摘要

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)‐4 H ‐1,3‐benzothiazin‐4‐one, C 20 H 23 F 3 N 4 O 3 S} 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 1 H NMR, 13 C 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 sp 2 ‐hybridization of the nitro N atom, which donates into the electron‐deficient 1,3‐benzothiazin‐4‐one group.