Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2

详细信息	查看全文 | 推荐本文 |

• 作者：Magda A.-A. El-Sayed^a ; Naglaa I. Abdel-Aziz^b ; ^{naglaabdalaziz2005@yahoo.com} ; Alaa A.-M. Abdel-Aziz^b ; ^c ; Adel S. El-Azab^c ; ^d ; Kamal E.H. ElTahir^e
• 关键词：Pyrazole ; Pyrazoline ; Synthesis ; COX-2 inhibitors ; Anti-inflammatory ; Molecular modeling
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 May, 2012
• 卷：20
• 期：10
• 页码：3306-3316
• 文件大小：971 K

摘要

New pyrazole and pyrazoline derivatives have been synthesized and their ability to inhibit ovine COX-1/COX-2 isozymes was evaluated using in vitro cyclooxygenase (COX) inhibition assay. Among the tested compounds, N-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)-3,5-bis(trifluoromethyl)aniline 8d exhibit optimal COX-2 inhibitory potency (IC₅₀ = 0.26 lM) and selectivity (SI) = >192.3] comparable with reference drug celecoxib (IC₅₀ value of 0.28 lM and selectivity index of 178.57). Moreover, the anti-inflammatory activity of selected compounds, which are the most selective COX-2 inhibitors in the COX inhibition assay, was investigated in vivo using carrageenan-induced rat paw edema model. Molecular modeling was conducted to study the ability of the active compounds to bind into the active site of COX-2 which revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.