Referenced in: none

Automatically associated channels: Kv11.1

Title: Scaffold-based design and synthesis of potent N-type calcium channel blockers.

Authors: Gerald W Zamponi, Zhong-Ping Feng, Lingyun Zhang, Hossein Pajouhesh, Yanbing Ding, Francesco Belardetti, Hassan Pajouhesh, David Dolphin, Lester A Mitscher, Terrance P Snutch

Journal, date & volume: Bioorg. Med. Chem. Lett., 2009 Nov 15 , 19, 6467-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19815411

Abstract
The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel.