SYNTHESIS OF SOME 1-(3-HYDROXY-4-METHOXYBENZYL)-2-ALKYL-6,7-METHYLENEDIOXY-1,2,3,4-TETRAHYDROISOQUINOLINES AND THEIR BINDING AFFINITIES TO DA RECEPTOR SUBTYPES

1-(3-Hydroxy-4-methoxybenzyl)-2-alkyl-6,7-methylenedioxytetrahydroisoquinolines (3a-c), derived from the D-1 selective antagonist S-bulbocapnine by cleavage of the bond between the 2 aromatic moieties, have been synthesized and their in vitro affinity towards D-1 and D-2 receptors evaluated. Of the compounds tested, the 2-methyl derivative 3a while showing poor affinity towards D-1 receptors was able to inhibit the D-2 radioligand H-3-raclopride binding by 60% at 10(-5) M. Conformational analysis allows reasonable explanations of the loss of D-1-affinity of 3a with respect to the model.