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

• Published in: Bioorganic & medicinal chemistry letters 2016-01, Vol.26 (2), p.406-412
• Main Authors: Abdellatif, Khaled R.A., Abdelall, Eman K.A., Fadaly, Wael A.A., Kamel, Gehan M.
• Format: Article
• Language: English
• Subjects: 1,5-Diarylpyrazole; Anti-inflammatory; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2 inhibitors; Humans; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazoline; Ulcer - chemically induced
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.11.105

[Display omitted] 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=99μmol/kg) which is approximately five folds more potent than ibuprofen (ED50=499μmol/kg) and had half potency of celecoxib (ED50=47μmol/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).