Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol

J Med Chem. 1991 Mar;34(3):1063-8. doi: 10.1021/jm00107a027.


The 2- and 6-fluoro derivatives of the potent beta-adrenergic agonist 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol were prepared and their adrenergic properties examined. The order of potency was as follows: beta-adrenergic activity (simulation of cyclic AMP formation in C6 glioma cells), 2-F = parent much greater than 6-F; beta 1-activity (rate of contraction, guinea pig atria), parent greater than 2-F much greater than 6-F; beta 2-activity (relaxation of guinea pig tracheal strip), 2-F greater than parent much greater than 6-F. The affinity of the 2-fluoro analogue for beta 1-adrenergic receptors (inhibition of the specific binding of [3H]dihydroalprenolol, rat cerebral cortical membranes) was 2 times greater, while the 6-fluoro analogue was 1450 times less than the parent. These results suggest that the aromatic rings of phenoxypropanolamine adrenergic agonists and phenylethanolamine adrenergic agonists bind in similar fashion to the adrenergic receptor, and that if interactions between fluorine and the side-chain hydroxyl group are critical in defining beta-adrenergic selectivity, the interactions are similar in both phenoxypropanolamines and phenylethanolamines.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / chemistry
  • Adrenergic beta-Agonists / metabolism
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Cell Membrane / metabolism
  • Cerebral Cortex / metabolism
  • Chemical Phenomena
  • Chemistry
  • Cyclic AMP / metabolism
  • Dihydroalprenolol / metabolism
  • Fluorine*
  • Glioma / metabolism
  • Guinea Pigs
  • Male
  • Molecular Structure
  • Muscle Relaxation / drug effects
  • Myocardial Contraction / drug effects
  • Propanolamines / chemistry
  • Propanolamines / metabolism
  • Propanolamines / pharmacology*
  • Rats
  • Receptors, Adrenergic, beta / metabolism
  • Structure-Activity Relationship
  • Trachea / drug effects
  • Trachea / physiology
  • Tumor Cells, Cultured


  • Adrenergic beta-Agonists
  • Propanolamines
  • Receptors, Adrenergic, beta
  • 2-fluoro-3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol
  • 3-(tert-butylamino)-1-(3,4-dihydroxy-6-fluorophenoxy)-2-propanol
  • Fluorine
  • Dihydroalprenolol
  • Cyclic AMP