Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,5-diarylpyrazole derivatives

摘要

A new series of 1,5-diarylpyrazoles 10a-l was designed and synthesized for evaluation as COX inhibitors and as anti-inflammatory agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 10e was the most COX-2 selective compound (S.I.=10.67) and the most potent anti-inflammatory derivative (ED50=46mol/kg) which is approximately 11-folds more potent than ibuprofen (ED50=499mol/kg) and had 2/3 potency of celecoxib (ED50=31mol/kg). All compounds were less ulcerogenic (ulcer indexes=1.20-4.61) than ibuprofen (ulcer index=20.25) and comparable to celecoxib (ulcer index=2.90).