Abstract
Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation on the aromatic A-region to analyze their effects on potency and efficacy (agonism versus antagonism). The halogenation caused enhanced functional antagonism at TRPV1 compared to the corresponding prototype agonists. The analysis of SAR indicated that the antagonism was enhanced as the size of the halogen increased (I>Br>Cl) and when the 6-position was halogenated. Compounds 23c and 31b were found to be potent full antagonists with K(i) (as functional antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively.
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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Bromine / chemistry
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CHO Cells
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Capsaicin / antagonists & inhibitors*
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Cricetinae
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Cricetulus
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Halogens / chemistry
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Iodine / chemistry
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Structure-Activity Relationship
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TRPV Cation Channels / agonists*
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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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Halogens
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N-(3-(tert-butylcarbonyloxy)-2-(3,4-dimethylbenzyl)propyl)-N'-(4-hydroxy-2,3-diiodo-5-methoxybenzyl)thiourea
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N-(4-tert-butylbenzyl)-N'-(4-hydroxy-2-bromo-3-iodo-5-methoxybenzyl)thiourea
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TRPV Cation Channels
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TRPV1 receptor
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Iodine
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Thiourea
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Capsaicin
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Bromine