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一系列取代的2-(1H-呋喃并[2,3-g]吲唑-1-基)乙胺衍生物作为5-HT2C受体激动剂的合成及构效关系

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.

作者信息

Shimada Itsuro, Maeno Kyoichi, Kazuta Ken-ichi, Kubota Hideki, Kimizuka Tetsuya, Kimura Yasuharu, Hatanaka Ken-ichi, Naitou Yuki, Wanibuchi Fumikazu, Sakamoto Shuichi, Tsukamoto Shin-ichi

机构信息

Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

出版信息

Bioorg Med Chem. 2008 Feb 15;16(4):1966-82. doi: 10.1016/j.bmc.2007.10.100. Epub 2007 Nov 4.

DOI:10.1016/j.bmc.2007.10.100
PMID:18035544
Abstract

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.

摘要

合成了一系列新型吲唑衍生物，并研究了它们的构效关系，以确定强效且选择性的5-HT2C受体激动剂。在这些化合物中，(S)-2-(7-乙基-1H-呋喃并[2,3-g]吲唑-1-基)-1-甲胺(YM348)具有良好的体外活性，即对人5-HT2C受体亚型具有高激动活性(EC50 = 1.0 nM)，且对5-HT2A受体具有高选择性。该化合物经口服给药时，在大鼠阴茎勃起模型中也有效。

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