Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT4 receptor agonists

被引：12

作者：

Itoh, K ^{[1
]}

Kanzaki, K ^{[1
]}

Ikebe, T ^{[1
]}

Kuroita, T ^{[1
]}

Tomozane, H ^{[1
]}

Sonda, S ^{[1
]}

Sato, N ^{[1
]}

Haga, K ^{[1
]}

Kawakita, T ^{[1
]}

机构：

[1] Yoshitomi Pharmaceut Ind Ltd, Res Labs, Fukuoka 8718550, Japan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1999年 / 34卷 / 11期

关键词：

5-HT4; receptor; 5-HT4 receptor agonist; structure-activity relationship; carboxamide; receptor model construction;

D O I：

10.1016/S0223-5234(99)00158-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT4 receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT4 receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT4 receptors than the other receptors, including, 5-HT3 and dopamine D-2 receptors. In addition, compound 24 was confirmed to be a potent 5-HT4 receptor agonist (ED50 = 7.0 nM). An interaction model between compound 24 and 5-HT4 receptor was proposed. (C) 1999 Editions scientifiques et medicales Elsevier SAS.

引用

页码：977 / 989

页数：13

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