Literature

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 [(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.

DOI： 10.1021/jm0709034

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

Journal of Medicinal Chemistry 2008.0

Discovery of (R)-9-Ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol- 6(2H)-one, a Selective, Orally Active Agonist of the 5-HT2CReceptor

Journal of Medicinal Chemistry 2007.0

Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays

Bioorganic & Medicinal Chemistry Letters 2020.0

Utilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT2CReceptor Agonists

Journal of Medicinal Chemistry 2017.0

Discovery of a novel azepine series of potent and selective 5-HT2C agonists as potential treatments for urinary incontinence

Bioorganic & Medicinal Chemistry Letters 2009.0

Pyrrolo(iso)quinoline derivatives as 5-HT2C receptor agonists