Abstract
A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant.
Keywords:
Capsaicin; Resiniferatoxin; TRPV1 antagonist; Vanilloid receptor 1.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Diterpenes / chemical synthesis*
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Diterpenes / chemistry
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Diterpenes / pharmacology*
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Humans
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Methylation
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Molecular Structure
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Protein Binding / drug effects
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Rats
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Stereoisomerism
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Structure-Activity Relationship
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TRPV Cation Channels / antagonists & inhibitors*
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Thiourea / analogs & derivatives
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Thiourea / chemical synthesis*
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Thiourea / chemistry
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Thiourea / pharmacology*
Substances
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Diterpenes
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TRPV Cation Channels
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resiniferatoxin
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Thiourea