Novel 5-[2-(N,N-di-n-propylamino)-ethyl]benzimidazole-derived high affinity dopaminergic ligands

Abstract

Derivatives of a noncatechol dopamine (DA) bioisostere 5-[2-(N,N-di-n-propylamino)ethyl]-benzimidazole (15) were synthesized and checked for affinity towards D-1 and D-2 DA receptors (DAR). Ten compounds were obtained by introducing groups of different inductive effects into position 2 of the parent compound 15, while two other compounds were synthesized by introducing a 1-naphthyl group into the side chain of dichloromethyl (9) and dibromomethyl (10) derivatives of 15. The affinity and selectivity of these novel compounds for the D-1 and D-2 class of the DAR were estimated by in vitro competition binding assays using synaptosomal membranes of the bovine caudate nuclei and [ 3 H]SCH 23390 (D-1 selective) and [ 3 H]spiperone (D-2 selective) as radioligands. None of the synthesized compounds expressed the affinity for the binding to D-1 receptors, while compounds 13, 14, 10, 9, 7 and 8, in this rank order of potencies competed with [ 3 H]spiperone binding to D-2 receptors under conditions of prevented radioligand binding to serotonin 5HT 2 receptors. Their affinities for this class of the DAR were about 2- to 555-fold higher in comparison to the parent compound 15, thus suggesting that some of them could be successfully used as dopaminergic ligands.