Alkylamino derivatives of N-benzylpyrazine-2-carboxamide: synthesis and antimycobacterial evaluation

Abstract

A series of alkylamino derivatives of N-benzylpyrazine-2-carboxamide was designed, synthesized and assayed in vitro for their antimycobacterial, antibacterial, antifungal as well as antiviral activities. Final structures were prepared from 6-chloro (1), 5-chloro (2) or 3-chloro (3) derivatives of N-benzylpyrazine-2-carboxamide by nucleophilic substitution of chlorine with n-alkylamines in the range from butylamine to octylamine (labelled a–e). Series 1a–e and 2a–e exerted higher activity against Mycobacterium tuberculosis H37Rv compared to the corresponding pattern compounds and the reference compound pyrazinamide. The most active derivatives reached an activity MIC = 4.6–10 μM (M. tbc H37Rv). More importantly, activity was also observed against other tested mycobacterial strains (including drug-resistant strains). Substitution of 3-chlorine was disadvantageous and led to completely inactive compounds 3a–e. Some compounds showed activity against Gram-positive bacterial strains (including MRSA) or influenza virus, but no antifungal activity was observed.