3-[5-(4,5-Dihydro-1H-imidazol-2-yl)-furan-2-yl]phenylamine (Amifuraline), a Promising Reversible and Selective Peripheral MAO-A Inhibitor

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• 作者：Francesco Gentili ; Nathalie Pizzinat ; Catherine Ordener ; Sophie Marchal-Victorion ; Agnè ; s Maurel ; Robert Hofmann ; Pierre Renard ; Philippe Delagrange ; Maria Pigini ; Angelo Parini ; Mario Giannella
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：September 7, 2006
• 年：2006
• 卷：49
• 期：18
• 页码：5578 - 5586
• 全文大小：315K
• 年卷期：v.49,no.18(September 7, 2006)
• ISSN：1520-4804

文摘

On the basis of the observation that the central side effects of MAO inhibitors may represent a major limitfor their use in pathological processes involving peripheral MAOs, we investigated the possibility of generatingnovel inhibitors able to target specifically peripheral MAOs. To address this issue, we designed compounds7-28. From biological results, the 2-(5-phenyl-furan-2-yl)-4,5-dihydro-1H-imidazole (Furaline, 17) provedto be a suitable lead. In fact, in enzyme assays on homogenate preparation from rat liver and HEK cellsexpressing MAO-A or MAO-B, compounds possessing the frame of 17 behaved as selective and reversibleMAO-A inhibitors. Interestingly, in in vivo studies the amino derivative 21 (Amifuraline), endowed withgood hydrophilic character, was able to significantly inhibit liver but not brain MAO-A.