SYNTHESIS OF FLUORODOPAMINES - EFFECT OF ARYL FLUORO SUBSTITUENTS ON AFFINITIES FOR ADRENERGIC AND DOPAMINERGIC RECEPTORS

Monofluorine-substituted dopamines (1b-d) have been prepared previousl y. Synthetic routes to di- and trifluorinated dopamines (1e-h) were ba sed on side chain elaboration of precursor fluorinated veratraldehydes . Binding data indicate that a 6-fluoro substituent decreases affinity at D-1-, D-2-, D-3- and D-4-dopamine receptors with the reduction (14 -fold) being greatest at the D-2-dopamine receptor. A 2-fluoro or 5-fl uoro substituent had little or no effect. Additional 2- and/or 5-fluor o substituents further reduced affinity of 6-fluorodopamine for dopami ne receptors. At adrenergic receptors, mono-fluoro substituents had on ly modest (2-fold or less) effects on affinity, while 2,6-di-, and 5,6 -difluoro substitution modestly decreased affinity. 2,5,6-Trifluorodop amine had very low affinity.