Synthesis of 1-substituted analogues of trimetoquinol possessing differential and selective beta-adrenergic properties

J Med Chem. 1977 Nov;20(11):1502-4. doi: 10.1021/jm00221a029.

Abstract

The synthesis of the 1,1-disubstituted tetrahydroisoquinoline analogues, 1-methyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (2) and 1-benzyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3), is described. The profile of beta-adrenergic activity for these analogues was determined and compared to that of trimetoquinol (1) in isolated guinea pig atrial, tracheal, and rat adipocyte preparations. Unexpected selective beta1-blocking activity in guinea pig trachea was noted with analogue 3. With the exception of 2 in guinea pig atria, 2 and 3 did not possess any beta-stimulant activity. Substitution at the 1 position of trimetoquinol (1) has revealed qualitative differences in beta-adrenergic activity.

MeSH terms

  • Adipose Tissue / metabolism
  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Antagonists / chemical synthesis*
  • Animals
  • Female
  • Guinea Pigs
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Isoquinolines / chemical synthesis*
  • Lipid Metabolism
  • Male
  • Muscle Relaxation
  • Muscle, Smooth / drug effects
  • Rats
  • Tretoquinol / analogs & derivatives
  • Tretoquinol / chemical synthesis*
  • Tretoquinol / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Isoquinolines
  • Tretoquinol