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Bioorg Med Chem Lett. 2012 Jun 15;22(12):4153-8. doi: 10.1016/j.bmcl.2012.04.054. Epub 2012 Apr 19.

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

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1
Zalicus Pharmaceuticals Ltd, 301-2389 Health Sciences Mall, Vancouver, BC, Canada.

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.

PMID:
22579422
DOI:
10.1016/j.bmcl.2012.04.054
[Indexed for MEDLINE]
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