Synthesis, Resolution, and Renal Vasodilation Activity of Novel DA₁ Agonists : 4-(3, 4-Dihydroxyphenyl)-1, 2, 3, 4-tetrahydroisoquinoline Derivatives

Abstract

7, 8-Dihydroxy-4-(3, 4-dihydroxyphenyl)-1, 2, 3, 4-tetrahydroisoquinoline (1) and 4-(3, 4-dihydroxyphenyl)-7-hydroxy-8-methyl-1, 2, 3, 4-tetrahydroisoquinoline (2) are potent renal vasodilators which selectively stimulate DA₁ (peripheral dopamine receptor-1) receptors. Especially, (S)-(-)-1 is the most potent. Its DA₁ agonist activity is about 10 times stronger than dopamine for increasing renal blood flow in anesthetized dogs. The renal and cardiovascular effects of (S)-(-)-1 may be suitable for the treatment of patients with renal insufficiency, heart failure and hypertension.