Potential Antiarrhythmic Agents III: 4-Amino-N-[ 2- (substituted amino) ethyl]-2,6-dimethylbenzamides
作者:D.K. Yung、E.K.F. Lo、M.M. Vohra
DOI:10.1002/jps.2600611213
日期:——
4-Amino-N-(2-morpholinoethyl)-2,6-dimethylbenzamide, 4-amino-N-(2-piperidinoethyl)-2,6-dimethylbenzamide, 4-amino-N-[2-(4-phenyl-1-piperazino)ethyl]-2,6-dimethylbenzamide, and 4-amino-N-[2-(3-azabicyclo[3.2.2]nonano)ethyl]-2,6-dimethylbenzamide were synthesized as potential antiarrhythmic agents. These compounds were found to be capable of prolonging the effective refractory period of the isolated
4-氨基-N-(2-吗啉代乙基)-2,6-二甲基苯甲酰胺,4-氨基-N-(2-哌啶子基乙基)-2,6-二甲基苯甲酰胺,4-氨基-N- [2-(4-苯基-合成了1-哌嗪子基)乙基] -2,6-二甲基苯甲酰胺和4-氨基-N- [2-(3-氮杂双环[3.2.2]壬诺)乙基] -2,6-二甲基苯甲酰胺作为潜在的抗心律不齐药。发现这些化合物能够延长分离的兔心房的有效不应期。他们还展示了针对哇巴因的预防活性。另外,4-氨基-N-(2-哌啶子基乙基)-2,6-二甲基苯甲酰胺能够终止哇巴因引起的心律失常,而4-氨基-N-(2-吗啉代乙基)-2,6-二甲基苯甲酰胺在其中活跃。拮抗乌头碱引起的心律失常。四种化合物,尤其是4-氨基-N- [2-(3-氮杂双环[3.2.2]壬诺)乙基] -2,6-二甲基苯甲酰胺,在兔子的角膜反射试验中也显示出一定程度的局部麻醉活性。测定了化合物的pKa和LD50值。