EFFECT OF FLUORINE SUBSTITUTION ON THE AGONIST SPECIFICITY OF NOREPINEPHRINE

Substitution of fluorine for hydrogen in position 2, 5, or 6 of the aromatic ring of norepinephrine markedly alters the α- and β-adrenergic agonist properties of norepinephrine. The 6-fluoro isomer is an α-adrenergic agonist with virtually no β agonist activity, while the 2-fluoro isomer is a β-adrenergic agonist with little α activity. The 5-fluoro isomer is equipotent with norepinephrine as an α agonist and significantly more potent as a β agonist. The possible physiochemical basis for these differences is discussed. Copyright © 1979 AAAS.