Polymorphism and Whole-Molecule Disorder of an Antitubercular 8-Nitrobenzothiazinone

Abstract

8-Nitrobenzo-1,3-thiazin-4-ones (BTZs) are a promising class of antitubercular agents with a novel mechanism of action, viz. suicide inhibition of decaprenylphosphoryl-β-D-ribose 2’-epimerase 1 (DprE1), an enzyme crucial for cell wall synthesis in the pathogen Mycobacterium tuberculosis. 8-Nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo-1,3-thiazin-4-one (1) is a chemically simplified analogue of the anti-tuberculosis phase 2 clinical drug candidate BTZ-043. Structural elucidation of 1 in the solid-state has been carried out by X-ray crystallography and two polymorphic forms of 1 have been revealed. 1-I crystallizes in the triclinic system (space group P-1, Z = 6) with one molecule exhibiting whole-molecule disorder with a preferred orientation. The crystal structure of 1-II belongs to the tetragonal system (space group P43, Z = 4) and exhibits positional disorder in several parts of the molecule.