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.