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

Abstract

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 = 46 μmol/kg) which is approximately 11-folds more potent than ibuprofen (ED₅₀ = 499 μmol/kg) and had 2/3 potency of celecoxib (ED₅₀ = 31 μmol/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).