Abstract
A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemistry*
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Amides / pharmacokinetics
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Amides / therapeutic use
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Analgesics / chemical synthesis
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Analgesics / pharmacokinetics
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Analgesics / therapeutic use
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Animals
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Binding Sites
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Furans / chemistry
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Half-Life
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Heterocyclic Compounds / chemistry*
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Hyperalgesia / chemically induced
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Hyperalgesia / drug therapy
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Male
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Molecular Docking Simulation
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Protein Structure, Tertiary
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / genetics
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TRPV Cation Channels / antagonists & inhibitors*
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TRPV Cation Channels / genetics
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TRPV Cation Channels / metabolism
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Thiourea / chemistry
Substances
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Amides
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Analgesics
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Furans
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Heterocyclic Compounds
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Recombinant Proteins
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TRPV Cation Channels
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Thiourea
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furan