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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2007-7-19
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pubmed:abstractText |
The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BayburtErol KEK,
pubmed-author:BrownBrian SBS,
pubmed-author:DiDomenicoStanleyS,
pubmed-author:DrizinIreneI,
pubmed-author:FaltynekConnie RCR,
pubmed-author:GeorgeKaren StKS,
pubmed-author:GomtsyanArthurA,
pubmed-author:HonorePriscaP,
pubmed-author:JarvisMichael FMF,
pubmed-author:JinkersonTammieT,
pubmed-author:KeddyRyan GRG,
pubmed-author:KoenigJohn RJR,
pubmed-author:LeeChih-HungCH,
pubmed-author:LukinKurillK,
pubmed-author:MarshKennan CKC,
pubmed-author:McDonaldHeath AHA,
pubmed-author:MikusaJoeJ,
pubmed-author:PernerRichard JRJ,
pubmed-author:SchmidtRobert GRG,
pubmed-author:TurnerSean CSC,
pubmed-author:WetterJill MJM,
pubmed-author:ZhengGuo ZhuGZ
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3651-60
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pubmed:meshHeading |
pubmed-meshheading:17583335-Administration, Oral,
pubmed-meshheading:17583335-Analgesics,
pubmed-meshheading:17583335-Animals,
pubmed-meshheading:17583335-Biological Availability,
pubmed-meshheading:17583335-Dogs,
pubmed-meshheading:17583335-Drug Stability,
pubmed-meshheading:17583335-Humans,
pubmed-meshheading:17583335-Indazoles,
pubmed-meshheading:17583335-Isoquinolines,
pubmed-meshheading:17583335-Microsomes, Liver,
pubmed-meshheading:17583335-Phenylurea Compounds,
pubmed-meshheading:17583335-Rats,
pubmed-meshheading:17583335-Structure-Activity Relationship,
pubmed-meshheading:17583335-TRPV Cation Channels,
pubmed-meshheading:17583335-Urea
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pubmed:year |
2007
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pubmed:articleTitle |
In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists.
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pubmed:affiliation |
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA. richard.j.perner@abbott.com
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pubmed:publicationType |
Journal Article,
In Vitro
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