Abstract
A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode.
Keywords:
Analgesic; Capsaicin; Resiniferatoxin; TRPV1 antagonists.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amides / chemistry*
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Amides / metabolism
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Amides / therapeutic use
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Analgesics / chemistry*
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Analgesics / metabolism
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Analgesics / therapeutic use
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Animals
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Benzeneacetamides / chemistry*
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Benzeneacetamides / metabolism
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Benzeneacetamides / therapeutic use
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Binding Sites
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Disease Models, Animal
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Humans
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Mice
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Molecular Docking Simulation
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Neuralgia / drug therapy
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Protein Binding
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Protein Structure, Tertiary
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Pyridines / chemistry*
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Rats
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonamides / metabolism
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Sulfonamides / therapeutic use
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TRPV Cation Channels / antagonists & inhibitors*
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TRPV Cation Channels / metabolism
Substances
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Amides
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Analgesics
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Benzeneacetamides
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N-((2-(cyclohexylthio)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(methylsulfonamido)phenyl)propanamide
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Pyridines
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Sulfonamides
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TRPV Cation Channels
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TRPV1 protein, human
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pyridine