Cross P E, Arrowsmith J E, Thomas G N, Gwilt M, Burges R A, Higgins A J
Pfizer Central Research, Sandwich, Kent, United Kingdom.
J Med Chem. 1990 Apr;33(4):1151-5. doi: 10.1021/jm00166a011.
A series of bis(arylalkyl)amines is described and their effects on prolonging effective refractory period in isolated cardiac tissue listed. Most compounds prolonged the cardiac action potential without significantly altering the maximum rate of depolarization and may be defined as selective class III antiarrhythmic agents. It was found that a particularly advantageous structural feature was to have a methanesulfonamido moiety on both of the aryl rings. Thus, compound 16 [1-(4-methanesulfonamidophenoxy)2-[N-(4-methanesulfonamidophene thyl)-N- methylamine]ethane] was selected for further investigations. The compound is highly potent and selective class III agent which acts by blockade of cardiac potassium channels.
本文描述了一系列双(芳基烷基)胺,并列出了它们对离体心脏组织有效不应期延长的影响。大多数化合物延长了心脏动作电位,而没有显著改变最大去极化速率,可被定义为选择性III类抗心律失常药物。发现一个特别有利的结构特征是在两个芳环上都有甲磺酰胺基部分。因此,选择化合物16 [1-(4-甲磺酰胺基苯氧基)-2-[N-(4-甲磺酰胺基苯乙基)-N-甲胺]乙烷]进行进一步研究。该化合物是一种高效且选择性的III类药物,通过阻断心脏钾通道发挥作用。