THE SEROTONIN 5-HT4 RECEPTOR .1. DESIGN OF A NEW CLASS OF AGONISTS AND RECEPTOR MAP OF THE AGONIST RECOGNITION SITE

被引：58

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/jm00013a009

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

The design and synthesis of a new class of potent and selective 5-HT4 receptor agonists containing an indole nucleus linked to a carbazimidamide are presented. A conformational study of the 5-HT4 receptor agonists serotonin and zacopride led to the identification of an initial pharmacophore and to the definition of a three-dimensional map of the 5-HT4 agonist recognition site. 1, a representative member of our new class of 5-HT4 receptor agonists, incorporates all reference structural features and matched perfectly with these models. 1 is a highly potent, full agonist at 5-HT4 receptors present in the isolated electrically stimulated guinea pig ileum preparation, with a pD(2) value of 8.8, displaying selectivity (ranging from 40-to over 10 000-fold) versus other members of the serotonin receptor family.

引用

页码：2326 / 2330

页数：5

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