Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity

Brian M Smith; Jeffrey M Smith; James H Tsai; Jeffrey A Schultz; Charles A Gilson; Scott A Estrada; Rita R Chen; Douglas M Park; Emily B Prieto; Charlemagne S Gallardo; Dipanjan Sengupta; William J Thomsen; Hazel R Saldana; Kevin T Whelan; Frederique Menzaghi; Robert R Webb; Nigel R A Beeley

doi:10.1016/j.bmcl.2004.12.080

Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity

Bioorg Med Chem Lett. 2005 Mar 1;15(5):1467-70. doi: 10.1016/j.bmcl.2004.12.080.

Authors

Brian M Smith¹, Jeffrey M Smith, James H Tsai, Jeffrey A Schultz, Charles A Gilson, Scott A Estrada, Rita R Chen, Douglas M Park, Emily B Prieto, Charlemagne S Gallardo, Dipanjan Sengupta, William J Thomsen, Hazel R Saldana, Kevin T Whelan, Frederique Menzaghi, Robert R Webb, Nigel R A Beeley

Affiliation

¹ Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, CA 92121-3223, USA. bsmith@arenapharm.com

PMID: 15713408
DOI: 10.1016/j.bmcl.2004.12.080

Abstract

We report on the synthesis, biological evaluation and structure-activity relationships for a series of 3-benzazepine derivatives as 5-HT(2C) receptor agonists. The compounds were evaluated in functional assays measuring [3H] phosphoinositol turnover in HEK-293 cells transiently transfected with h5-HT(2C), h5-HT(2A) or h5-HT(2B) receptors. Several compounds are shown to be potent and selective 5-HT(2C) receptor agonists, which decrease food intake in a rat feeding model.

MeSH terms

Animals
Benzazepines* / chemical synthesis
Benzazepines* / pharmacology
Benzazepines* / therapeutic use
Cell Line
Disease Models, Animal
Drug Evaluation, Preclinical
Eating / drug effects
Humans
Male
Molecular Structure
Obesity / drug therapy*
Rats
Rats, Sprague-Dawley
Serotonin 5-HT2 Receptor Agonists*
Structure-Activity Relationship

Substances

Benzazepines
Serotonin 5-HT2 Receptor Agonists