Synthesis and binding properties of several new dopaminergic ligands

Four different heterocyclic dopamine bioisosteres were synthesized. The affinity and selectivity of these compounds for the D-1 and D-2 classes of the dopamine receptor were determined in competition binding experiments using synaptosomal membranes from bovine caudate nuclei and [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) as radioligands. None of these compounds expressed significant affinity for the D-1 receptors, while compounds 3, 4, 2 and 1 in this order of potency strongly competed with [3H]spiperone binding to D-2 receptors under conditions that prevented radioligand binding to serotonin 5HT2 receptors (50 nM ketanserin). Compounds 3 and 4 behave as agonists as judged by the data obtained in competition binding experiments in the presence of Gpp(NH)p, the former (3) expressing a very high affinity for D-2 receptors.