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

The discovery and structure–activity relationship (SAR) studies of a novel class of sodium channel blockers are disclosed. 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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2005-06, Vol.15 (11), p.2943-2947
Main Authors: Liang, Jun, Brochu, Richard M., Cohen, Charles J., Dick, Ivy E., Felix, John P., Fisher, Michael H., Garcia, Maria L., Kaczorowski, Gregory J., Lyons, Kathryn A., Meinke, Peter T., Priest, Birgit T., Schmalhofer, William A., Smith, McHardy M., Tarpley, Jason W., Williams, Brande S., Martin, William J., Parsons, William H.
Format: Article
Language:English
Subjects:
Analgesics
Biological and medical sciences
Chronic Disease
Humans
Medical sciences
Molecular Conformation
Molecular Probes
Neuropharmacology
Pain - drug therapy
Pharmacology. Drug treatments
Sodium Channel Blockers - chemistry
Sodium Channel Blockers - therapeutic use
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Summary:The discovery and structure–activity relationship (SAR) studies of a novel class of sodium channel blockers are disclosed. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2005.02.093