THE SEROTONIN 5-HT4 RECEPTOR .2. STRUCTURE-ACTIVITY STUDIES OF THE INDOLE CARBAZIMIDAMIDE CLASS OF AGONISTS

被引：82

作者：

BUCHHEIT, KH ^{[1
]}

GAMSE, R ^{[1
]}

GIGER, R ^{[1
]}

HOYER, D ^{[1
]}

KLEIN, F ^{[1
]}

KLOPPNER, E ^{[1
]}

PFANNKUCHE, HJ ^{[1
]}

MATTES, H ^{[1
]}

机构：

[1] SANDOZ PHARMA LTD,PRECLIN RES,CH-4002 BASEL,SWITZERLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 13期

关键词：

D O I：

10.1021/jm00013a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A number of substituted indole carbazimidamides were prepared and evaluated as 5-HT4 receptor agonists by using the isolated field-stimulated guinea pig ileum preparation. Their selectivity for the 5-HT4 receptor was established by examining their affinity for other 5-HT receptors using radioligand-binding techniques. Several selective and highly potent full as well as partial agonists emerged from this study. For example, 1b,d were found to be the most potent, full 5-HT4 receptor agonists described so far (EC(50) = 0.5 and 0.8 nM, respectively), being 6 and 4 times more potent than serotonin itself. On the other hand, 5b and 1h appeared as partial 5-HT4 receptor agonists in the nonstimulated guinea pig ileum preparation with potencies, evaluated against serotonin action, respectively similar (5b, K-i = 12 nM) to and 300-fold higher (1h, K-i = 0.04 nM) than serotonin.

引用

页码：2331 / 2338

页数：8

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