Discovery and Structure− Activity Relationship of (1 R)-8-Chloro-2, 3, 4, 5-tetrahydro-1-methyl-1 H-3-benzazepine (Lorcaserin), a Selective Serotonin 5-HT2C …

…, EB Prieto, CS Gallardo, D Sengupta…

Index: 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. Journal of Medicinal Chemistry, 2008 , vol. 51, # 2 p. 305 - 313

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Citation Number: 150

Abstract

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 ...