Design and synthesis of 3-(4-aminophenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide/carbothioamide analogues as antitubercular agents

Emergence of multi-drug resistant tuberculosis (MDR-TB) and HIV-TB co-infections potentiate the development of newer antitubercular agents to combat against tuberculosis, a dreadful disease. In the present investigation a series of pyrazoline analogues were designed and synthesized based on the structure of known antitubercular agent thiacetazone, in hope of obtaining new and safe antitubercular agents. The target molecules were synthesized in two steps, starting with the condensation of 4-aminoacetophenone and p-anisidine in methanolic sodium hydroxide solution followed by the cyclization of intermediate chalcones with appropriate semicarbazide/thiosemicarbazide in glacial acetic acid. All the synthesized compounds were characterized by 1H NMR, IR and mass spectral data and the purity of the compounds was checked by elemental analysis. Their antimycobacterial activity was evaluated by two folds serial dilution method. 3-(4-Aminophenyl)-N-(4-chlorophenyl)-4,5-dihydro-5-(4-methoxyphenyl)pyrazole-1-carboxamide (4i) showed maximum activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of 7.41 μM.