| Literature DB >> 19815411 |
Gerald W Zamponi1, Zhong-Ping Feng, Lingyun Zhang, Hossein Pajouhesh, Yanbing Ding, Francesco Belardetti, Hassan Pajouhesh, David Dolphin, Lester A Mitscher, Terrance P Snutch.
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.Entities:
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Year: 2009 PMID： 19815411 DOI： 10.1016/j.bmcl.2009.09.008
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823