New tetrahydrobenzindoles as potent and selective 5-HT7 antagonists with increased in vitro metabolic stability

被引：23

作者：

Kikuchi, C ^{[1
]}

Suzuki, H ^{[1
]}

Hiranuma, T ^{[1
]}

Koyama, M ^{[1
]}

机构：

[1] Meiji Seika Kaisha Ltd, Pharmaceut Res Ctr, Kohoku Ku, Yokohama, Kanagawa 2228567, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 01期

关键词：

D O I：

10.1016/S0960-894X(02)00842-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Chemical modifications of compound 1 (DR4004), a potent, selective antagonist of the 5-HT7 receptor, were conducted with the aim of improving its metabolic stability. Halogenation of putative sites of oxidative metabolism afforded compounds 7-10, which retained high affinity and selectivity for the 5-HT7 receptor, and showed increased in vitro metabolic stability. Compound 10 (DR4485) showed oral bioavailability, and should be a useful tool for evaluating the therapeutic potential of 5-HT7 antagonists. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：61 / 64

页数：4

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