An anomalous effect of N-isopropyl substitution in determining beta-adrenergic activity

Drug Des Deliv. 1988 May;2(4):257-62.

Abstract

We report unexpected results in an investigation of cyclic analogues of dopamine and norepinephrine possessing the structures 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (3) and 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthalenol (7). N-Isopropyl substitution of these compounds, providing 4 and 8, brings about the total disappearance of their stimulant activity on beta-adrenergic receptors. On the basis of current knowledge about the structure-activity relationship of adrenergic drugs, it is difficult to provide an explanation for these results; however a tentative rationalization based on conformational considerations is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Propanol
  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Agonists / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Drug Design
  • Guinea Pigs
  • In Vitro Techniques
  • Indicators and Reagents
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Rats
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / metabolism
  • Structure-Activity Relationship

Substances

  • Adrenergic beta-Agonists
  • Indicators and Reagents
  • Receptors, Adrenergic, beta
  • 1-Propanol