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

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.

Graphical abstractThe discovery and structure–activity relationship (SAR) studies of a novel class of sodium channel blockers are disclosed.Figure optionsDownload full-size imageDownload as PowerPoint slide