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rdf:type |
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lifeskim:mentions |
umls-concept:C0028754,
umls-concept:C0053917,
umls-concept:C0087111,
umls-concept:C0220781,
umls-concept:C0243072,
umls-concept:C0243192,
umls-concept:C0268563,
umls-concept:C0541284,
umls-concept:C1527178,
umls-concept:C1705938,
umls-concept:C1883254
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pubmed:issue |
7
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pubmed:dateCreated |
2010-3-22
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pubmed:abstractText |
This Letter describes a series of potent and selective BRS-3 agonists containing a biarylethylimidazole pharmacophore. Extensive SAR studies were carried out with different aryl substitutions. This work led to the identification of a compound 2-{2-[4-(pyridin-2-yl)phenyl]ethyl}-5-(2,2-dimethylbutyl)-1H-imidazole 9 with excellent binding affinity (IC(50)=18 nM, hBRS-3) and functional agonist activity (EC(50)=47 nM, 99% activation). After oral administration, compound 9 had sufficient exposure in diet induced obese mice to demonstrate efficacy in lowering food intake and body weight via BRS-3 activation.
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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 |
Apr
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:DobbelaarPeter HPH,
pubmed-author:GoodmanAllanA,
pubmed-author:GuanXiao-MingXM,
pubmed-author:GuoChengC,
pubmed-author:GuzzoPeter RPR,
pubmed-author:HaddenMarkM,
pubmed-author:HeShuwenS,
pubmed-author:HendersonAlan JAJ,
pubmed-author:HowardAndrew DAD,
pubmed-author:JianTianyingT,
pubmed-author:KanYanqingY,
pubmed-author:KellyTheresa MTM,
pubmed-author:LEET CTC,
pubmed-author:LinLinus SLS,
pubmed-author:LiuJianJ,
pubmed-author:MarshDonald JDJ,
pubmed-author:MetzgerJoseph MJM,
pubmed-author:NargundRavi PRP,
pubmed-author:PalyhaOksanaO,
pubmed-author:PattamanaKevinK,
pubmed-author:PengQianpingQ,
pubmed-author:ReitmanMarc LML,
pubmed-author:RuenzMeganM,
pubmed-author:SargentBruce JBJ,
pubmed-author:SebhatIyassu KIK,
pubmed-author:SwensonBrianB,
pubmed-author:TamvakopoulosConstantinC,
pubmed-author:WyvrattMatthew JMJ,
pubmed-author:YetLarryL
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pubmed:copyrightInfo |
2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
20
|
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
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pubmed:pagination |
2074-7
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pubmed:meshHeading |
pubmed-meshheading:20219372-Animals,
pubmed-meshheading:20219372-Body Weight,
pubmed-meshheading:20219372-Eating,
pubmed-meshheading:20219372-Humans,
pubmed-meshheading:20219372-Imidazoles,
pubmed-meshheading:20219372-Mice,
pubmed-meshheading:20219372-Obesity,
pubmed-meshheading:20219372-Rats,
pubmed-meshheading:20219372-Receptors, Bombesin,
pubmed-meshheading:20219372-Structure-Activity Relationship
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pubmed:year |
2010
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pubmed:articleTitle |
Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. jian_liu@merck.com
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pubmed:publicationType |
Journal Article
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