Kaiho T, San-Nohe K, Kajiya S, Suzuki T, Otsuka K, Ito T, Kamiya J, Maruyama M
Pharmaceuticals Department, Mitsui Toatsu Chemicals Inc., Yokohama, Japan.
J Med Chem. 1989 Feb;32(2):351-7. doi: 10.1021/jm00122a012.
A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure. Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series.
合成了一系列1-甲基-7-(4-吡啶基)-5,6,7,8-四氢-3(2H)-异喹啉酮及其相关化合物，并对其正性肌力活性进行了评估。该系列的大多数成员在犬急性心力衰竭模型中使心肌收缩力呈剂量依赖性增加，而它们仅引起心率和血压的轻微变化。几种衍生物，特别是在4-位带有氰基、乙酰基和乙基取代基的衍生物，比用作参考的米力农更有效。4-乙酰基-1-甲基-7-(4-吡啶基)-5,6,7,8-四氢-3(2H)-异喹啉酮(MS-857)是该系列中最有效的正性肌力药物之一。
