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

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• 作者：Khaled R.A. Abdellatif^a ; ^{khaled.ahmed@pharm.bsu.edu.eg" class="auth_mail" title="E-mail the corresponding author} ; Eman K.A. Abdelall^a ; Wael A.A. Fadaly^a ; Gehan M. Kamel^b
• 关键词：Anti-inflammatory ; Pyrazoline ; 1 ; 5-Diarylpyrazole ; Cyclooxygenase-2 inhibitors
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：26
• 期：2
• 页码：406-412
• 全文大小：531 K

文摘

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