Synthesis of novel pyrazole-thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors

A series of 1,3,4-trisubstituted pyrazole derivatives (3a-f), (4a-f), and (5a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, H-1 NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 mu M. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 mu M), with a significant selectivity index (SI >60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents. (C) 2014 Elsevier Ltd. All rights reserved.