Pajouhesh, HassanFeng, Zhong-PingZhang, LingyunPajouhesh, HosseinJiang, XinpoDong, HaihengDing, YanbingPorreca, FrankBelardetti, FrancescoHendricson, Adam W.Tringham, Elizabeth W.Vanderah, Todd W.Zamponi, Gerald W.Mitscher, Lester A.Snutch, Terrance Preston2018-05-292018-05-292012-04-19Pajouhesh, H., Feng, Z. P., Zhang, L., Pajouhesh, H., Jiang, X., Hendricson, A., … Snutch, T. P. (2012). Structure-activity relationships of trimethoxybenzyl piperazine N-type calcium channel inhibitors. Bioorganic and Medicinal Chemistry Letters, 22(12), 4153–4158. https://doi.org/10.1016/j.bmcl.2012.04.054http://hdl.handle.net/1880/10669710.11575/PRISM/43761We 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.enhttps://creativecommons.org/licenses/by/4.0journal articlehttp://dx.doi.org/10.1016/j.bmcl.2012.04.054