Syntheses and Adrenergic Activities of Ring-Fluorinated Epinephrines

J Med Chem. 1988 Oct;31(10):1972-7. doi: 10.1021/jm00118a019.

Abstract

The study of chemical and biological effects of fluorine substitution on the aromatic ring of catecholamines has now been extended to epinephrine (Epi). 2- and 6-fluoroepinephrines (2-FEpi and 6-FEpi) have been synthesized. Fluorine substitution on the 2- or 6-carbon of the aromatic ring alters the selectivity of epinephrine toward alpha- and beta-adrenergic receptors, similar in manner to the change in selectivity seen with norepinephrine (NE). Thus, 2-FEpi is a relatively selective beta-adrenergic ligand, while 6-FEpi is a relatively selective alpha-adrenergic ligand. Fluorine substitution of Epi also can markedly increase potency at either alpha- or beta-adrenergic receptors.

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Animals
  • Cerebral Cortex / metabolism
  • Cyclic AMP / metabolism
  • Dihydroalprenolol / metabolism
  • Dioxanes / metabolism
  • Epinephrine / analogs & derivatives*
  • Epinephrine / pharmacology
  • Guinea Pigs
  • Rats
  • Receptors, Adrenergic, alpha / metabolism*
  • Receptors, Adrenergic, beta / metabolism*

Substances

  • Adenylyl Cyclase Inhibitors
  • Dioxanes
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Dihydroalprenolol
  • Cyclic AMP
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
  • Epinephrine