Discovery of a “True” Aspirin Prodrug

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• 作者：Louise M. Moriarty ; Maeve N. Lally ; Ciaran G. Carolan ; Michael Jones ; John M. Clancy ; John F. Gilmer
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：December 25, 2008
• 年：2008
• 卷：51
• 期：24
• 页码：7991-7999
• 全文大小：275K
• 年卷期：v.51,no.24(December 25, 2008)
• ISSN：1520-4804

文摘

Aspirin prodrugs formed by derivatization at the benzoic acid group are very difficult to obtain because the promoiety accelerates the rate of hydrolysis by plasma esterases at the neighboring acetyl group, generating salicylic acid derivatives. By tracing the hydrolysis pattern of the aspirin prodrug isosorbide-2,5-diaspirinate (ISDA) in human plasma solution, we were able to identify a metabolite, isosorbide-2-aspirinate-5-salicylate, that undergoes almost complete conversion to aspirin by human plasma butyrylcholinesterase, making it the most successful aspirin prodrug discovered to date.