Structural characterization and antimycobacterial evaluation of a benzimidazole analogue of the antituberculosis clinical drug candidate TBA-7371

Abstract

The crystal structure and in vitro antimycobacterial properties of N-(2-fluoroethyl)-1-[(6-methoxy-5-methylpyrimidin-4-yl)methyl]-1H-benzo[d]imidazole-4-carboxamide (C17H18FN5O2, 1), a previously reported benzimidazole analogue of the 1,4-azaindole-based antituberculosis drug candidate TBA-7371, are reported. The structure determination was achieved using Hirshfeld atom refinement. Compound 1 crystallizes in the triclinic system (space group P\overline{1}) with two molecules in the asymmetric unit (Z′ = 2). The two crystallographically distinct molecules exhibit a similar conformation with the amide groups in a Z conformation, forming an intramolecular Namide—H...Nbenzimidazole hydrogen bond. The most significant supramolecular feature in the solid-state is a relatively short Cbenzimidazole—H...Npyrimidine hydrogen bond. Antimycobacterial testing confirmed in vitro activity against Mycobacterium smegmatis, but no growth inhibtion of Mycobacterium abscessus was found.