Synthesis and antimycobacterial evaluation of new gem- difluorohydrazides

Abstract

Several gem-difluorohydrazides were prepared by the addition of nitrogen nucleophiles to N-acetyl-2,2-gem-difluoroxindoles substituted in position 5. Initially, commercial isatin was N-acetylated using acetic anhydride. The subsequent step was the chemoselective difluorination of the carbonyl ketone employing DAST, giving the gem-difluoroxindoles in moderate yields. Finally, the product obtained was subjected to ring opening reaction with different nucleophiles. The twelve products obtained are novel and were evaluated for antimycobacterial activity against Mycobacterium tuberculosis. Five of these compounds showed good antimicrobial activity, two of them, are more potent than the drugs of first choice for the treatment of TB, ethambutol and pyrazinamide. Furthermore, the active compounds did not show cytotoxicity.

Keywords

• tuberculosis
• isoniazid
• difluorhydrazides