Synthesis, Cyclooxygenase Inhibition, Anti‐Inflammatory Evaluation, and Ulcerogenic Liability of New 1,3,5‐Triarylpyrazoline Derivatives Possessing a Methanesulfonyl Pharmacophore

Abstract

A new series of 1,3,5-triarylpyrazolines 13a-l was synthesized and all prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and in vivo anti-inflammatory activity. All test compounds were more selective for the COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 13h was the most COX-2 selective compound (COX-2 selectivity index (SI) = 10.23) and the most potent anti-inflammatory derivative (ED50 = 60.1 µmol/kg) in comparison with celecoxib (COX-2 SI = 9.29 and ED50 = 81.4 µmol/kg). All screened compounds were less ulcerogenic (ulcer indexes (UI) = 0.33-1.33) than aspirin (UI = 2.33) and comparable to celecoxib (UI = 0.33).