Details

Autor(en) / Beteiligte

• Smith, Brian M
• Smith, Jeffrey M
• Tsai, James H
• Schultz, Jeffrey A
• Gilson, Charles A
• Estrada, Scott A
• Chen, Rita R
• Park, Douglas M
• Prieto, Emily B
• Gallardo, Charlemagne S
• Sengupta, Dipanjan
• Dosa, Peter I
• Covel, Jon A
• Ren, Albert
• Webb, Robert R
• Beeley, Nigel R. A
• Martin, Michael
• Morgan, Michael
• Espitia, Stephen
• Saldana, Hazel R
• Bjenning, Christina
• Whelan, Kevin T
• Grottick, Andrew J
• Menzaghi, Frederique
• Thomsen, William J

Titel

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

Ist Teil von

• Journal of medicinal chemistry, 2008-01, Vol.51 (2), p.305-313

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 [3H]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 (t 1/2 = 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.