Abstract
Novel cyclopentane-based 3-phenyl-1-hydroxypropyl compounds were evaluated for inhibitory activity against the peripheral nerve sodium channel Na(V)1.7 and off-target activity against the cardiac potassium channel hERG. The stereochemistry of the hydroxyl group and substitution on the phenyl rings with either fluorinated O-alkyl or alkyl groups were found to be critical for conferring potency against Na(V)1.7. A benchmark compound from this series displayed efficacy in rat models of inflammatory and neuropathic pain.
MeSH terms
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Animals
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Cyclopentanes / chemical synthesis
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Cyclopentanes / chemistry*
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Cyclopentanes / pharmacokinetics
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Cyclopentanes / pharmacology*
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Inhibitory Concentration 50
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Molecular Structure
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Rats
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Sodium Channel Blockers / chemical synthesis*
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Sodium Channel Blockers / chemistry
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Sodium Channel Blockers / pharmacokinetics
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Sodium Channel Blockers / pharmacology*
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Sodium Channels / metabolism*
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Structure-Activity Relationship
Substances
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Cyclopentanes
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Ether-A-Go-Go Potassium Channels
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Sodium Channel Blockers
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Sodium Channels