Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists.
A series of novel indazole derivatives were synthesized, and their structure-activity relationships examined in order to identify potent and selective 5-HT2C receptor agonists. Among these compounds, (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348) had a good in vitro profile, that is, high agonistic activity to the human 5-HT2C receptor subtype (EC50 = 1.0 nM) and high selectivity over 5-HT2A receptors. This compound was also effective in a rat penile erection model when administered p.o.
Shimada
Itsuro
I
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. itsuro.shimada@jp.astellas.com
Maeno
Kyoichi
K
Kazuta
Ken-ichi
K
Kubota
Hideki
H
Kimizuka
Tetsuya
T
Kimura
Yasuharu
Y
Hatanaka
Ken-ichi
K
Naitou
Yuki
Y
Wanibuchi
Fumikazu
F
Sakamoto
Shuichi
S
Tsukamoto
Shin-ichi
S
D000818:Animals; D005021:Ethylamines / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects; D051381:Rats; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D005021:Ethylamines; D007191:Indazoles; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists