Design, Synthesis and Pharmacological evaluation of 2,5 di phenyl 1,3,4-oxadiazole derivatives as selective COX-2 inhibitors

Abstract

A novel series of substituted-2,5-diphenyl-1,3,4-oxadiazole derivatives (3a-i) have been synthesized with the aim to get better anti-inflammatory and selective cox -2 inhibitor activity. Compound (2a-i) was reacted with several aryl acid hydrazides in phosphorousoxychloride to obtain the title compounds. Structures of the synthesized compounds were supported by means of IR, 1 H NMR and mass spectroscopy.All synthesized derivatives were determined by the carrageenan induced rat paw oedema model for Anti-inflammatory activity. The entire compound gives good response for anti-inflammatory activity for this activity indomethacine was used as standard drug and compared to new synthesized drugs. Some New Synthesized drugs have to shown better activities for anti-inflammatory. Title compounds were evaluated for their anti-inflammatory and selective cox-2 activities. These compounds also exhibited significant anti-inflammatory activity, which is comparable to that of celecoxib in the carrageenan-induced rat paw edema method. The selected compounds were evaluated for their preliminary in vitro cyclooxygenase inhibitory activity against COX-2 and COX-1 enzymes. The compounds tested showed selective inhibitory activity toward COX-2(72-5%) over COX-1 (3.5%)., amongst them compounds 3c and 3i showed appreciable COX-2 selective inhibitory activity.