5,7-Dihydroxy-2-aminotetralin derivatives: synthesis and assessment of dopaminergic and adrenergic actions

J Med Chem. 1981 Feb;24(2):149-53. doi: 10.1021/jm00134a005.

Abstract

Replacement of the catechol 3,4-dihydroxylation pattern of certain adrenergic beta-phenethylamines by a resorcinol 3,5-dihydroxylation pattern has led to a greater selectivity of adrenergic agonist effects in certain molecules. This strategy has been applied to a series of dopaminergic agents derived from 2-aminotetralin, leading to a 5,7-dihydroxylation pattern. Traditional literature approaches to formation of a tetralin ring with this oxygenation pattern failed. A method was used which involved cyclization of 3,5-dimethoxybenzylsuccinic acid derivatives with pyridinium poly(HF) and subsequent modification of the tetralin ring. The resorcinol-derived 2-aminotetralins were less potent and less active dopaminergic agents than their catechol-derived isomers (5,6-dihydroxy and/or 6,7-dihydroxy). Certain of the subject compounds demonstrated alpha- and beta 1-adrenoceptor activating properties.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cats
  • Chemical Phenomena
  • Chemistry
  • Dogs
  • Dopamine / physiology*
  • Female
  • Guinea Pigs
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Male
  • Mice
  • Naphthalenes / chemical synthesis*
  • Rats
  • Receptors, Adrenergic / drug effects
  • Receptors, Dopamine / drug effects
  • Sympathomimetics / chemical synthesis*
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Naphthalenes
  • Receptors, Adrenergic
  • Receptors, Dopamine
  • Sympathomimetics
  • Tetrahydronaphthalenes
  • 5,7-dihydroxy-2-aminotetralin
  • Dopamine