Synthesis and structure-activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists.
To identify potent and selective 5-HT(2C) receptor agonists, a series of novel benzazepine derivatives were synthesized, and their structure-activity relationships examined. The compounds were evaluated for their 5-HT(2C), 5-HT(2A), and 5-HT(2B) receptor binding affinity and intrinsic activity for the 5-HT(2C) and 5-HT(2A) receptors. Among these compounds, 6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine (6) was effective in a rat penile erection model when administered po, which is a symptom of the serotonin syndrome reflecting 5-HT(2C) receptor activation. Moreover, compound 6 was characterized as a partial agonist of 5-HT(2A) receptors; therefore, it had little effect on the cardiovascular system.
Shimada
Itsuro
I
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. itsuro.shimada@jp.astellas.com
Maeno
Kyoichi
K
Kondoh
Yutaka
Y
Kaku
Hidetaka
H
Sugasawa
Keizo
K
Kimura
Yasuharu
Y
Hatanaka
Ken-ichi
K
Naitou
Yuki
Y
Wanibuchi
Fumikazu
F
Sakamoto
Shuichi
S
Tsukamoto
Shin-ichi
S
D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects; D058826:Serotonin 5-HT2 Receptor Agonists; D013329:Structure-Activity Relationship
D001552:Benzazepines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D058826:Serotonin 5-HT2 Receptor Agonists