Reference
Pajouhesh, Hassan, et al. “Structure-Activity Relationships of Trimethoxybenzyl Piperazine N-Type Calcium Channel Inhibitors”. Bioorg Med Chem Lett, vol. 22, no. 12, Jan. 2012, pp. 4153-8, https://doi.org/10.1016/j.bmcl.2012.04.054.
Abstract
We previously reported the small organic N-type calcium channel blocker NP078585 that while efficacious in animal models for pain, exhibited modest L-type calcium channel selectivity and substantial off-target inhibition against the hERG potassium channel. Structure-activity studies to optimize NP078585 preclinical properties resulted in compound 16, which maintained high potency for N-type calcium channel blockade, and possessed excellent selectivity over the hERG (~120-fold) and L-type (~3600-fold) channels. Compound 16 shows significant anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain and is also efficacious in the rat formalin model of inflammatory pain.