Abstract
A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics, Non-Narcotic / chemical synthesis
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Analgesics, Non-Narcotic / chemistry
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Analgesics, Non-Narcotic / metabolism
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Analgesics, Non-Narcotic / pharmacology*
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Anilides / chemical synthesis
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Anilides / chemistry
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Anilides / metabolism
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Anilides / pharmacology*
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Binding, Competitive
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Calcium Channel Blockers / chemical synthesis
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / metabolism
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Calcium Channel Blockers / pharmacology*
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Calcium Channels, N-Type / chemistry
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Calcium Channels, N-Type / metabolism*
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Calcium Signaling / drug effects
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Cell Line, Tumor
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Drug Design*
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Fluorobenzenes / chemical synthesis
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Fluorobenzenes / chemistry
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Fluorobenzenes / metabolism
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Fluorobenzenes / pharmacology
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High-Throughput Screening Assays
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Humans
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Molecular Structure
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Molecular Targeted Therapy
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Nerve Tissue Proteins / antagonists & inhibitors*
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Nerve Tissue Proteins / metabolism
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Neuralgia / drug therapy
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Neuralgia / metabolism
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Neurons / drug effects*
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Neurons / metabolism
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Neurotoxins / chemistry
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Pain, Intractable / drug therapy
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Pain, Intractable / metabolism
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Structure-Activity Relationship
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omega-Conotoxin GVIA / chemistry
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omega-Conotoxin GVIA / metabolism
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omega-Conotoxin GVIA / pharmacology
Substances
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Analgesics, Non-Narcotic
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Anilides
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CACNA1B protein, human
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Calcium Channel Blockers
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Calcium Channels, N-Type
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Fluorobenzenes
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Nerve Tissue Proteins
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Neurotoxins
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omega-Conotoxin GVIA