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Bioorg Med Chem Lett. 2012 Jun 15;22(12):4080-3. doi: 10.1016/j.bmcl.2012.04.075. Epub 2012 May 2.

A novel series of pyrazolylpiperidine N-type calcium channel blockers.

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  • 1Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA.


Selective blockers of the N-type calcium channel have proven to be effective in animal models of chronic pain. However, even though intrathecally delivered synthetic ω-conotoxin MVIIA from Conus magnus (ziconotide [Prialt®]) has been approved for the treatment of chronic pain in humans, 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. In vivo efficacy in rat models of inflammatory and neuropathic pain was demonstrated by a representative compound from this series.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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