Synthesis, resolution, and renal vasodilation activity of novel DA1 agonists: 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives.
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.
Anan
H
H
Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Tanaka
A
A
Tsuzuki
R
R
Yokota
M
M
Yatsu
T
T
Honda
K
K
Asano
M
M
Fujita
S
S
Furuya
T
T
Fujikura
T
T
D000818:Animals; D004285:Dogs; D018492:Dopamine Antagonists; D006439:Hemodynamics / Q000187:drug effects; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D017447:Receptors, Dopamine D1; D012079:Renal Circulation / Q000187:drug effects*; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents / Q000494:pharmacology*
D018492:Dopamine Antagonists; D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; C073506:4-(3,4-dihydroxyphenyl)-7-hydroxy-8-methyl-1,2,3,4-tetrahydroisoquinoline; C073504:zelandopam