Design and pharmacological activity of phosphinic acid based NAALADase inhibitors
Design and pharmacological activity of phosphinic acid based NAALADase inhibitors
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DOI：
10.1021/jm0001774
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发表时间：
2001-11-22
影响因子：
7.3
通讯作者：
Slusher, BS
中科院分区：
文献类型：
--
作者：
Jackson, PF;Tays, KL;Slusher, BS
本工作描述了一系列新的基于次膦酸的神经肽酶NAALADase抑制剂。这一系列化合物是迄今为止所描述的最有效的酶抑制剂系列。此外，我们已经证明这些化合物在神经变性的动物模型中具有保护作用。化合物34显著防止脑缺血的大脑中动脉闭塞模型中的神经变性。此外，在神经性疼痛的慢性收缩模型中，化合物34显著减弱了用盐水处理的动物观察到的超敏反应。这些数据表明，NAALADase抑制可能为神经退行性疾病和周围神经病变的治疗提供一种新的方法。
A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive mc del of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.