Synthesis and dopaminergic features of six novel 3-arylpiperidines

Abstract

Four substituted 3-aryl-1-{2-[5-(1H-benzimidazole)]ethyl}piperidines and two 3-aryl-1-{2-[6-(1,4-dihydroxyquinoxaline-2,3-dione)]ethyl} piperidines were synthesized, characterized and evaluated for in vitro binding affinity at the D1 and D2 dopamine and 5-HT1A serotonin receptors using synaptosomal membranes of fresh bovine caudate nuclei and hippocampi as a source of the dopamine and serotonin receptors, respectively, and the corresponding specific radioligands. All six novel compounds expressed no binding affinity at the D1 and 5-HT1A receptors. Derivatives of 1,4- dihydroxyquinoxaline-2,3-dione (compounds 8a and 8b) and of 2- dihalomethylbenzimidazole (ligands 9 and 10) were moderate competitors of [ 3 H]spiperone binding at the D2 dopamine receptors. However, benzimidazole- 2-thiones (compounds 7a and 7b) behaved as selective D2 receptor ligands with the binding affinity in the nanomolar range of concentrations.