Synthesis and Antiarrhythmic Activity of Disubstituted Phenylpyridine Derivative.
作者:Hiromichi SHIGYO、Seiichi SATO、Kimiyuki SHIBUYA、Yoshio TAKAHASHI、Takashi YAMAGUCHI、Hiroyuki SONOKI、Tomio OHTA
DOI:10.1248/cpb.41.1573
日期:——
disubstituted phenylpyridine derivatives was synthesized and their antiarrhythmic effects against chloroform-induced ventricular arrhythmias in mice were examined. Among them, 2- and 3-[2-(3-aminobutyramido)-4-(2,2,2-trifluroethoxy)phenyl]pyri dines (23h, 24h) and 3-[2-(3-aminobutyramido)-4-ethoxyphenyl]pyridine (24i) showed potent antiarrhythmic activity. They had approximately twice the potency of mexiletine
合成了一系列双取代的苯基吡啶衍生物,并研究了它们对氯仿诱导的小鼠心律失常的抗心律失常作用。其中,2-和3- [2-(3-氨基丁酰胺基)-4-(2,2,2-三氟乙氧基)苯基]嘧啶二烯(23h,24h)和3- [2-(3-氨基丁酰胺基)-4 -乙氧基苯基]吡啶(24i)显示有效的抗心律不齐活性。他们具有美西律(III)效力的大约两倍。从该系列中选择化合物24i作为进一步开发的候选化合物;它被发现具有IB类电生理特性,并显示出心肌中钠通道的慢速依赖于速率的阻滞(RDB)。