Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain

Jun Liang; Richard M. Brochu; Charles J. Cohen; Ivy E. Dick; John P. Felix; Michael H. Fisher; Maria L. Garcia; Gregory J. Kaczorowski; Kathryn A. Lyons; Peter T. Meinke; Birgit T. Priest; William A. Schmalhofer; McHardy M. Smith; Jason W. Tarpley; Brande S. Williams; William J. Martin; William H. Parsons

doi:10.1016/j.bmcl.2005.02.093

Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain

Jun Liang, Richard M. Brochu, Charles J. Cohen, Ivy E. Dick, John P. Felix, Michael H. Fisher, Maria L. Garcia, Gregory J. Kaczorowski, Kathryn A. Lyons, Peter T. Meinke, Birgit T. Priest, William A. Schmalhofer, McHardy M. Smith, Jason W. Tarpley, Brande S. Williams, William J. Martin, William H. Parsons

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

A new series of voltage-gated sodium channel blockers with potential for treatment of chronic pain is reported. Systematic structure-activity relationship studies, starting with compound 1, led to identification of potent analogs that displayed use-dependent block of sodium channels, were efficacious in pain models in vivo, and most importantly, were devoid of activity against the cardiac potassium channel hERG.

Original language	English (US)
Pages (from-to)	2943-2947
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2005.02.093
State	Published - Jun 2 2005
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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10.1016/j.bmcl.2005.02.093

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Liang, J., Brochu, R. M., Cohen, C. J., Dick, I. E., Felix, J. P., Fisher, M. H., Garcia, M. L., Kaczorowski, G. J., Lyons, K. A., Meinke, P. T., Priest, B. T., Schmalhofer, W. A., Smith, M. M., Tarpley, J. W., Williams, B. S., Martin, W. J., & Parsons, W. H. (2005). Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain. Bioorganic and Medicinal Chemistry Letters, 15(11), 2943-2947. https://doi.org/10.1016/j.bmcl.2005.02.093

Liang, J, Brochu, RM, Cohen, CJ, Dick, IE, Felix, JP, Fisher, MH, Garcia, ML, Kaczorowski, GJ, Lyons, KA, Meinke, PT, Priest, BT, Schmalhofer, WA, Smith, MM, Tarpley, JW, Williams, BS, Martin, WJ & Parsons, WH 2005, 'Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain', Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 11, pp. 2943-2947. https://doi.org/10.1016/j.bmcl.2005.02.093

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title = "Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain",

abstract = "A new series of voltage-gated sodium channel blockers with potential for treatment of chronic pain is reported. Systematic structure-activity relationship studies, starting with compound 1, led to identification of potent analogs that displayed use-dependent block of sodium channels, were efficacious in pain models in vivo, and most importantly, were devoid of activity against the cardiac potassium channel hERG.",

author = "Jun Liang and Brochu, {Richard M.} and Cohen, {Charles J.} and Dick, {Ivy E.} and Felix, {John P.} and Fisher, {Michael H.} and Garcia, {Maria L.} and Kaczorowski, {Gregory J.} and Lyons, {Kathryn A.} and Meinke, {Peter T.} and Priest, {Birgit T.} and Schmalhofer, {William A.} and Smith, {McHardy M.} and Tarpley, {Jason W.} and Williams, {Brande S.} and Martin, {William J.} and Parsons, {William H.}",

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doi = "10.1016/j.bmcl.2005.02.093",

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AU - Liang, Jun

AU - Brochu, Richard M.

AU - Cohen, Charles J.

AU - Dick, Ivy E.

AU - Felix, John P.

AU - Fisher, Michael H.

AU - Garcia, Maria L.

AU - Kaczorowski, Gregory J.

AU - Lyons, Kathryn A.

AU - Meinke, Peter T.

AU - Priest, Birgit T.

AU - Schmalhofer, William A.

AU - Smith, McHardy M.

AU - Tarpley, Jason W.

AU - Williams, Brande S.

AU - Martin, William J.

AU - Parsons, William H.

PY - 2005/6/2

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Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain

Abstract

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