Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,3,5-triarylpyrazoline and 1,5-diarylpyrazole derivatives as selective COX-2 inhibitors

Two new series of 1,3,5-triarylpyrazolines 10a-m and 1,5-diarylpyrazoles 14a-d were synthesized. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 10k was the most COX-2 selective compound (S.I. = 5.91) and the most potent anti-inflammatory derivative (ED50 = 99 mu mol/kg) which is approximately five folds more potent than ibuprofen (ED50 = 499 mu mol/kg) and had half potency of celecoxib (ED50 = 47 mu mol/kg). All compounds were less ulcerogenic (Ulcer Indexes = 1.20-5.00) than ibuprofen (Ulcer Index = 20.25) and comparable to celecoxib (Ulcer Index = 2.90). (C) 2015 Elsevier Ltd. All rights reserved.