1383544-07-7Relevant articles and documents
A novel series of pyrazolylpiperidine N-type calcium channel blockers
Subasinghe, Nalin L.,Wall, Mark J.,Winters, Michael P.,Qin, Ning,Lubin, Mary Lou,Finley, Michael F.A.,Brandt, Michael R.,Neeper, Michael P.,Schneider, Craig R.,Colburn, Raymond W.,Flores, Christopher M.,Sui, Zhihua
, p. 4080 - 4083 (2012/07/03)
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.