Referenced in: none

Automatically associated channels: Kv11.1

Title: Structure-activity relationships of trimethoxybenzyl piperazine N-type calcium channel inhibitors.

Authors: Hassan Pajouhesh, Zhong-Ping Feng, Lingyun Zhang, Hossein Pajouhesh, Xinpo Jiang, Adam Hendricson, Haiheng Dong, Elizabeth Tringham, Yanbing Ding, Todd W Vanderah, Frank Porreca, Francesco Belardetti, Gerald W Zamponi, Lester A Mitscher, Terrance P Snutch

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Jun 15 , 22, 4153-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22579422

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.