Document Report Card

ID: ALA1134287

Journal: J Med Chem

Title: Design and pharmacological activity of phosphinic acid based NAALADase inhibitors.

Authors: Jackson PF, Tays KL, Maclin KM, Ko YS, Li W, Vitharana D, Tsukamoto T, Stoermer D, Lu XC, Wozniak K, Slusher BS.

Abstract: 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 model 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.

CiteXplore: 11708918

DOI: 10.1021/jm0001774