Synthesis and antimycobacterial screening of new N-(4-(5-aryl-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)-4-amide derivatives

This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-(4-(5-aryl-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)-4-amide derivatives (8a-x). The antitubercular activity of the compounds against Mycobacterium tuberculosis H(37)Rv (MTB) revealed that 2-chloro-N-(4-(5-(4-chlorophenyl)-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)benzamide (8n) is the most promising lead molecule with a MIC of 1.56 mu g/mL, while the corresponding unsubstituted benzamide derivative (8o) is the next most active molecule with a MIC of 3.13 mu g/mL. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity (MIC = 3.13 mu g/mL). Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development. (C) 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.