Design, synthesis and biological evaluation of diarylpyrazole/triazole bearing 1,3,4- oxadiazole moiety as coxs inhibitors endowed with potential anti-inflammatory and analgesic activities

A novel series of diarylpyrazole/triazole derivatives linked to 1,3,4-oxadiazole moiety was synthesized and evaluated in vitro against COX-1/COX-2 enzymes and in vivo for their both anti-inflammatory/analgesic activities utilizing carrageenan-induced paw edema technique and Acetic-acid induced writhing procedure, respectively. The results revealed that compound 13a with adamantyl residue linked to 1,5-diaryl pyrazole showed the highest anti-inflammatory activity comparing with the other derivatives in the series. In comparison to celecoxib, 13a exhibited approximately half the anti-inflammatory activity and selectivity against COX-2 isoenzyme (EI% = 39.18 and IC50 (COX-2) = 2.52 μM for 13a; EI% = 82.71 and IC50 (COX-2) = 0.95 μM for celecoxib). Finally, the binding interactions of 13a into the active site of COX-2 isozyme was explained by performing a docking study.