Kanojia R M, Lever O W, Press J B, Williams L, Werblood H M, Giardino E C, Falotico R, Tobia A J
Research Laboratories, Ortho Pharmaceutical Corporation, Raritan, New Jersey 08869.
J Med Chem. 1989 May;32(5):990-7. doi: 10.1021/jm00125a011.
The synthesis and cardiovascular evaluation of a series of isoquinolin-3-ol derivatives bearing a variety of nitrogen substituents (amino, acylamino, carbamate, and ureido) at C-4 are described. Certain of these compounds have a selective renal vasodilating profile and have minimal effects on arterial blood pressure or heart rate when administered intravenously in the instrumented anesthetized dog. The most potent renal vasodilator in the series is 4-(allylureido)-6,7-dimethoxyisoquinolin-3-ol (38), which at a dose of 1.2 mg/kg iv produces a 97% maximal increase in renal blood flow without significant hypotensive or chronotropic effects. Structure-activity observations on the nature of the 4-substituent and the alkoxy substitution pattern in the aromatic ring of the isoquinolinol nucleus are discussed.
本文描述了一系列在C-4位带有各种氮取代基（氨基、酰氨基、氨基甲酸酯和脲基）的异喹啉-3-醇衍生物的合成及其心血管评估。其中某些化合物具有选择性肾血管舒张作用，在麻醉的插管犬静脉给药时，对动脉血压或心率的影响极小。该系列中最有效的肾血管舒张剂是4-(烯丙基脲基)-6,7-二甲氧基异喹啉-3-醇（38），静脉注射剂量为1.2mg/kg时，可使肾血流量最大增加97%，且无明显的降压或变时作用。讨论了关于异喹啉醇核芳香环中4-取代基的性质和烷氧基取代模式的构效关系观察结果。
