NO-Donor COX-2 Inhibitors. New Nitrooxy-Substituted 1,5-Diarylimidazoles Endowed with COX-2 Inhibitory and Vasodilator Properties

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• 作者：Konstantin Chegaev ; Loretta Lazzarato ; Paolo Tosco ; Clara Cena ; Elisabetta Marini ; Barbara Rolando ; Pierre-Alain Carrupt ; Roberta Fruttero ; Alberto Gasco
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：April 5, 2007
• 年：2007
• 卷：50
• 期：7
• 页码：1449 - 1457
• 全文大小：244K
• 年卷期：v.50,no.7(April 5, 2007)
• ISSN：1520-4804

文摘

A series of NO-donor diarylimidazoles derived from the lead compound Cimicoxib were synthesized andevaluated for their COX-2 inhibitory activity and their stability in whole blood as well as for vasodilatorproperties. The products are partly transformed into the corresponding alcohols following 24-h incubationin whole blood. All of them display good COX-1/COX-2 selectivity, but are less potent than the lead; amolecular modeling study was carried out to investigate their binding mode. The compounds are also capableof relaxing rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism; this propertycould confer reduced cardiotoxicity with respect to traditional COX-2 inhibitors.