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

doi:10.1021/jm0001774

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 journal › Article › peer-review

80 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4170-4175
Number of pages	6
Journal	Journal of medicinal chemistry
Volume	44
Issue number	24
DOIs	https://doi.org/10.1021/jm0001774
State	Published - Nov 22 2001
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Design and pharmacological activity of phosphinic acid based NAALADase inhibitors",

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.",

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

year = "2001",

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doi = "10.1021/jm0001774",

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T1 - Design and pharmacological activity of phosphinic acid based NAALADase inhibitors

AU - Jackson, P. F.

AU - Tays, K. L.

AU - Maclin, K. M.

AU - Ko, Y. S.

AU - Li, W.

AU - Vitharana, D.

AU - Tsukamoto, T.

AU - Stoermer, D.

AU - Lu, X. C.M.

AU - Wozniak, K.

AU - Slusher, B. S.

PY - 2001/11/22

Y1 - 2001/11/22

N2 - 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.

AB - 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.

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Design and pharmacological activity of phosphinic acid based NAALADase inhibitors

Abstract

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