2a-[4-(tetrahydropyridoindol-2-yl)butyl]tetrahydrobenzindole derivatives:: New selective antagonists of the 5-hydroxytryptamine7 receptor

被引：51

作者：

Kikuchi, C ^{[1
]}

Ando, T ^{[1
]}

Watanabe, T ^{[1
]}

Nagaso, H ^{[1
]}

Okuno, M ^{[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：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 11期

关键词：

D O I：

10.1021/jm0104264

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tetrahydrobenzindoles was prepared, and the affinity of these compounds for the 5-hydroxytryptamine(7) (5-HT7) receptor and other receptors was evaluated. Most of the compounds showed high affinity for the 5-HT7 receptor, and 2a-[4-(tetrahydropyridoindol-2-yl)butyl]tetrahydrobenzindole derivatives (26a-j) exhibited high selectivity for this receptor. The nature of the substituent at the 9-position of the tetralrydropyridindole ring affected the affinity for the 5-HT7 receptor, and the 9-carbamoyl moiety afforded increased selectivity. Compound 26j exhibited high affinity for the 5-HT7 receptor, with at least 280-fold selectivity over the 5-HT2 receptor. In a functional model of 5-HT7 receptor activation, this compound was confirmed to have 5-HT7 receptor antagonist activity. It should be a useful tool for clarifying the biological role of the 5-HT7 receptor.

引用

页码：2197 / 2206

页数：10

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