4-(allylureido)-6,7-dimethoxyisoquinolin-3-ol is a potent and selective renal vasodilator in a canine model, increasing renal blood flow without affecting systemic blood pressure or heart rate.
Hypothesis-generating for selective renal vasodilation without systemic effects; leaves open translation to human cardiorenal disease.
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.
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Kanojia et al. (1989) studied this question.
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