Conformationally Defined Adrenergic Agents. 2. Catechol Imidazoline Derivatives: Biological Effects at α1 and α2 Adrenergic Receptors

Article abstract of DOI:10.1021/jm00154a006

The synthesis and pharmacology of 2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline (A-54741, 4), a very potent α-adrenergic agonist, are described.The change in biological activity resulting from variation of the carboxylic 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 α₁- and α₂-adrenergic receptors.Compound 4 was found in vitro to be a full agonist with greater potency at the α₂ receptor (ED50 norepinephrine (NE)/ED50 4 = 188 +/- 22) than at the α₁ receptor (ED50 NE/ED50 4 = 13 +/- 2).