Design and pharmacological activity of phosphinic acid based NAALADase inhibitors

P. F. Jackson, K. L. Tays, K. M. Maclin, Y. S. Ko, W. Li, D. Vitharana, T. Tsukamoto, D. Stoermer, X. C.M. Lu, K. Wozniak, B. S. Slusher

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)4170-4175
Number of pages6
JournalJournal of medicinal chemistry
Issue number24
StatePublished - Nov 22 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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