Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents

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• 作者：Ghaneya Sayed Hassan^a ; Sahar Mahmoud Abou-Seri^a ; ^{saharshaarawy_69@yahoo.com" class="auth_mail} ; Gehan Kamel^b ; Mamdouh Moawad Ali^c
• 关键词：Celecoxib analogs ; Benzofuran ; Pyrazole ; Anti-inflammatory agents ; COX-1/COX-2 inhibitory activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：9 April, 2014
• 年：2014
• 卷：76
• 期：Complete
• 页码：482-493
• 全文大小：1227 K

文摘

Novel series of celecoxib analogs endowed with benzofuran moiety 3a-e and 9a-d were synthesized and evaluated for COX-1/COX-2 inhibitory activity in聽vitro. The most potent and selective COX-2 inhibitors - compounds 3c, 3d, 3e, 9c and 9d - were assessed for their anti-inflammatory activity and ulcerogenic liability in聽vivo. The 3-(pyridin-3-yl)pyrazole derivatives 3c and 3e exhibited the highest anti-inflammatory activity, that is equipotent to celecoxib. Furthermore, the tested compounds proved to have better gastric safety profile compared to celecoxib. In particular, compound 3e demonstrated about 40% reduction in ulcerogenic potential relative to the reference drug. Finally, molecular docking simulation of the new compounds in COX-2 active site and drug likeness studies showed good agreement with the obtained pharmaco-biological results.