取代酚类的合成及其抗心律失常和抗副交感神经特性。3. 连接区域（区域3）的修饰。

Synthesis and antiarrhythmic and parasympatholytic properties of substituted phenols. 3. Modifications to the linkage region (region 3).

作者信息

Stout D M, Matier W L, Barcelon-Yang C, Reynolds R D, Brown B S

出版信息

J Med Chem. 1985 Mar;28(3):295-8. doi: 10.1021/jm00381a006.

Abstract

As part of a continuing program of systematically modifying the structure of the class I antiarrhythmic drug changrolin, we synthesized 15 analogues in which the linkage between the two aromatic regions was altered. High antiarrhythmic activity and low parasympatholytic activity was found when the linkage region, designated region 3, contained a carbonyl moiety, including ketones, amides, and ureas. Secondary amides were superior to tertiary amides, while amide reversal resulted in no change in activities. One compound in this series, 7, 2,6-bis(1-pyrrolidinyl-methyl)-4-benzamidophenol (ACC-9358), is undergoing preclinical evaluations.

摘要

作为对I类抗心律失常药物常咯啉结构进行系统性修饰的持续项目的一部分，我们合成了15种类似物，其中两个芳香区域之间的连接部分发生了改变。当被指定为区域3的连接区域含有羰基部分（包括酮、酰胺和脲）时，发现具有高抗心律失常活性和低抗副交感神经活性。仲酰胺优于叔酰胺，而酰胺反转时活性无变化。该系列中的一种化合物，7,2,6-双（1-吡咯烷基甲基）-4-苯甲酰胺基苯酚（ACC-9358），正在进行临床前评估。