3-[5-(4,5-dihydro-1H-imidazol-2-yl)-furan-2-yl]phenylamine (amifuraline), a promising reversible and selective peripheral MAO-A Inhibitor
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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DOI：
10.1021/jm060605r
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发表时间：
2006-09-07
影响因子：
7.3
通讯作者：
Giannella, Mario
中科院分区：
文献类型：
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作者：
Gentili, Francesco;Pizzinat, Nathalie;Giannella, Mario
MAO 抑制剂的中枢副作用可能是其在涉及外周 MAO 的病理过程中使用的主要限制，基于这一观察，我们研究了产生能够特异性靶向外周 MAO 的新型抑制剂的可能性。为了解决这个问题，我们设计了化合物7-28。从生物学结果来看，2-(5-苯基-呋喃-2-基)-4,5-二氢-1H-咪唑（Furaline，17）被证明是合适的先导化合物。事实上，在对表达 MAO-A 或 MAO-B 的大鼠肝脏和 HEK 细胞制备的匀浆进行酶测定时，具有 17 框架的化合物表现为选择性和可逆的 MAO-A 抑制剂。有趣的是，在体内研究中，氨基衍生物21（Amifuraline）具有良好的亲水性，能够显着抑制肝脏而非大脑的MAO-A。
On the basis of the observation that the central side effects of MAO inhibitors may represent a major limit for their use in pathological processes involving peripheral MAOs, we investigated the possibility of generating novel inhibitors able to target specifically peripheral MAOs. To address this issue, we designed compounds 7-28. From biological results, the 2-( 5-phenyl-furan-2-yl)-4,5-dihydro-1H-imidazole ( Furaline, 17) proved to be a suitable lead. In fact, in enzyme assays on homogenate preparation from rat liver and HEK cells expressing MAO-A or MAO-B, compounds possessing the frame of 17 behaved as selective and reversible MAO-A inhibitors. Interestingly, in in vivo studies the amino derivative 21 ( Amifuraline), endowed with good hydrophilic character, was able to significantly inhibit liver but not brain MAO-A.