Selective blockers of the N-type calcium channel have proven to be effective in animal models of chronic pain. Even though intrathecally delivered synthetic w-conotoxin MVIIA from Conus magnus (ziconotide [Prialt�]) has been approved for the treatment of chronic pain, its mode of delivery and narrow therapeutic window have limited its usefulness. Therefore, the identification of orally active, small-molecule N-type calcium channel blockers would represent a significant advancement in the treatment of chronic pain. A novel series of pyrazole-based N-type calcium channel blockers was identified by structural modification of a high-throughput screening hit and further optimized to improve potency and metabolic stability. Here we describe the synthesis, and In vivo efficacy of this series of compounds.

Novel series of pyrazolylpiperidine N-type calcium channel blockers

244th National Meeting (2012)

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