Conformationally defined adrenergic agents. 2. Catechol imidazoline derivatives: biological effects at alpha 1 and alpha 2 adrenergic receptors

J Med Chem. 1986 Apr;29(4):463-7. doi: 10.1021/jm00154a006.

Abstract

The synthesis and pharmacology of 2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline (A-54741, 4), a very potent alpha-adrenergic agonist, are described. The change in biological activity resulting from variation of the carbocyclic ring size of 4 from four through seven members (2-5) is presented, as well as an explanation that accounts for this change in activity by considering the "exactness of fit" of these compounds to both the alpha 1- and alpha 2-adrenergic receptors. Compound 4 was found in vitro to be a full agonist with greater potency at the alpha 2 receptor (ED50 norepinephrine (NE)/ED50 4 = 188 +/- 22) than at the alpha 1 receptor (ED50 NE/ED50 4 = 13 +/- 2).

MeSH terms

  • Adrenergic alpha-Agonists / chemical synthesis
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Imidazoles / chemical synthesis
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Male
  • Molecular Conformation
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects*
  • Structure-Activity Relationship

Substances

  • Adrenergic alpha-Agonists
  • Imidazoles
  • Receptors, Adrenergic, alpha