Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity.
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.
Smith
Brian M
BM
Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, CA 92121-3223, USA. bsmith@arenapharm.com
Smith
Jeffrey M
JM
Tsai
James H
JH
Schultz
Jeffrey A
JA
Gilson
Charles A
CA
Estrada
Scott A
SA
Chen
Rita R
RR
Park
Douglas M
DM
Prieto
Emily B
EB
Gallardo
Charlemagne S
CS
Sengupta
Dipanjan
D
Thomsen
William J
WJ
Saldana
Hazel R
HR
Whelan
Kevin T
KT
Menzaghi
Frederique
F
Webb
Robert R
RR
Beeley
Nigel R A
NR
D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058826:Serotonin 5-HT2 Receptor Agonists; D013329:Structure-Activity Relationship
D001552:Benzazepines; D058826:Serotonin 5-HT2 Receptor Agonists