SYNTHESIS AND BIOLOGICAL ACTION OF THE AMINOTETRAHYDROISOQUINOCARBAZOLES AND RELATED-COMPOUNDS - A NEW CLASS OF COMPOUNDS WITH ANTIARRHYTHMIC ACTIVITY

被引：16

作者：

SHIMOJI, Y ^{[1
]}

TOMITA, K ^{[1
]}

HASHIMOTO, T ^{[1
]}

SAITO, F ^{[1
]}

MORISAWA, Y ^{[1
]}

MIZUNO, H ^{[1
]}

YORIKANE, R ^{[1
]}

KOIKE, H ^{[1
]}

机构：

[1] SANKYO CO LTD,SANKYO RES LABS,2-58 HIROMACHI 1-CHOME,SHINAGAWA KU,TOKYO 140,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 05期

关键词：

D O I：

10.1021/jm00083a004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 12-aminotetrahydroisoquinocarbazoles and related compounds were synthesized using an intramolecular Diels-Alder reaction and screened for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice. Several compounds showed more potent activity than disopyramide. There was some correlation between substituents on aromatic ring and angular position, and antiarrhythmic activity. An amino group or some functional groups containing an amino group on C-12 seemed to be essential to exhibit the activity. Ring size also influenced the activity. The compound (+)-10 (RS-2135) had the most favorable combination of antiarrhythmic activity and toxicity and was selected for further evaluation.

引用

页码：816 / 822

页数：7

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