Design and pharmacological activity of phosphinic acid based NAALADase inhibitors

被引：89

作者：

Jackson, PF ^{[1
]}

Tays, KL ^{[1
]}

Maclin, KM ^{[1
]}

Ko, YS ^{[1
]}

Li, WX ^{[1
]}

Vitharana, D ^{[1
]}

Tsukamoto, T ^{[1
]}

Stoermer, D ^{[1
]}

Lu, XCM ^{[1
]}

Wozniak, K ^{[1
]}

Slusher, BS ^{[1
]}

机构：

[1] Guilford Pharmaceut Inc, Baltimore, MD 21224 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 24期

关键词：

D O I：

10.1021/jm0001774

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：4170 / 4175

页数：6

共 23 条

[1]

BARRETT AJ, 1998, HDB PROTEOLYTIC ENZY, P1434

[2] A PERIPHERAL MONONEUROPATHY IN RAT THAT PRODUCES DISORDERS OF PAIN SENSATION LIKE THOSE SEEN IN MAN [J].