Abstract
A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC(50) values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Analgesics / chemical synthesis
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Analgesics / chemistry
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Analgesics / pharmacology
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Animals
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Benzhydryl Compounds / chemical synthesis*
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Benzhydryl Compounds / chemistry
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Benzhydryl Compounds / pharmacology
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Calcium Channel Blockers / chemical synthesis*
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / pharmacology
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Calcium Channels, N-Type / drug effects*
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Humans
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Inhibitory Concentration 50
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Molecular Structure
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Solubility
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Structure-Activity Relationship
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Water / chemistry
Substances
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1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one
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Analgesics
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Benzhydryl Compounds
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Calcium Channel Blockers
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Calcium Channels, N-Type
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Piperazines
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Water