Specific dopamine D-1 and DA1 properties of 4-(mono- and -dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline and its tetrahydrothieno[2,3c]pyridine analog

Authors:
  • RRRobert M. Riggs
    Robert M. Riggs
  • DNDavid E. Nichols
    David E. Nichols
  • MFMark M. Foreman
    Mark M. Foreman
  • LTLewis L. Truex
    Lewis L. Truex
  • DGDana Glock
    Dana Glock
  • JKJai D. Kohli
    Jai D. Kohli
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Abstract
The title compounds were prepared and examined to elucidate further the structure-activity relationships of dopamine agonists related to nomifensine. Two of the compounds, 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydrosoquinoline and 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydrothieno[2,3-c]pyridine, have been reported in the patent literature. In stimulation of rat retinal adenylate cyclase, ameasure of dopamine D-1 agonist activity, the tetrahydroisoquinoline was about equipotent to dopamine. The thienyl isostere had nearly twice the potency. Both compounds were potent vasodilators in the canine renal artery, producing dilation through stimulation of DA1 type peripheral dopamine receptors. A monohydroxy analogue, 4-(3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline, had only slight activity in the cyclase assay and was inactive in the canine renal artery. These results, combined with those from an earlier study, demonstrate that N-alkylation decreases both dopamine D-1 and DA-1 agonist potency with activity ordered as H > methyl > ethyl > propyl. The results also demonstrate the necessity for the catechol function in this series.
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