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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-17
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pubmed:abstractText |
The synthesis and SAR of a novel 3-benzazepine series of 5-HT2C agonists is described. Compound 7d (lorcaserin, APD356) was identified as one of the more potent and selective compounds in vitro (pEC50 values in functional assays measuring [(3)H]phosphoinositol turnover: 5-HT2C = 8.1; 5-HT2A = 6.8; 5-HT2B = 6.1) and was potent in an acute in vivo rat food intake model upon oral administration (ED50 at 6 h = 18 mg/kg). Lorcaserin was further characterized in a single-dose pharmacokinetic study in rat (t1/2 = 3.7 h; F = 86%) and a 28-day model of weight gain in growing Sprague-Dawley rat (8.5% decrease in weight gain observed at 36 mg/kg b.i.d.). Lorcaserin was selected for further evaluation in clinical trials for the treatment of obesity.
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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 |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BeeleyNigel R ANR,
pubmed-author:BjenningChristinaC,
pubmed-author:ChenRita RRR,
pubmed-author:CovelJon AJA,
pubmed-author:DosaPeter IPI,
pubmed-author:EspitiaStephenS,
pubmed-author:EstradaScott ASA,
pubmed-author:GallardoCharlemagne SCS,
pubmed-author:GilsonCharles ACA,
pubmed-author:GrottickAndrew JAJ,
pubmed-author:MartinMichaelM,
pubmed-author:MenzaghiFrederiqueF,
pubmed-author:MorganMichaelM,
pubmed-author:ParkDouglas MDM,
pubmed-author:PrietoEmily BEB,
pubmed-author:RenAlbertA,
pubmed-author:SaldanaHazel RHR,
pubmed-author:SchultzJeffrey AJA,
pubmed-author:SenguptaDipanjanD,
pubmed-author:SmithBrian MBM,
pubmed-author:SmithJeffrey MJM,
pubmed-author:ThomsenWilliam JWJ,
pubmed-author:TsaiJames HJH,
pubmed-author:WebbRobert RRR,
pubmed-author:WhelanKevin TKT
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
305-13
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18095642-Animals,
pubmed-meshheading:18095642-Anti-Obesity Agents,
pubmed-meshheading:18095642-Benzazepines,
pubmed-meshheading:18095642-Cell Line,
pubmed-meshheading:18095642-Eating,
pubmed-meshheading:18095642-Humans,
pubmed-meshheading:18095642-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:18095642-Male,
pubmed-meshheading:18095642-Obesity,
pubmed-meshheading:18095642-Rats,
pubmed-meshheading:18095642-Rats, Sprague-Dawley,
pubmed-meshheading:18095642-Serotonin 5-HT2 Receptor Agonists,
pubmed-meshheading:18095642-Stereoisomerism,
pubmed-meshheading:18095642-Structure-Activity Relationship,
pubmed-meshheading:18095642-Weight Gain
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pubmed:year |
2008
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pubmed:articleTitle |
Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity.
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pubmed:affiliation |
Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, California 92121, USA. bsmith@arenapharm.com
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pubmed:publicationType |
Journal Article
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