6-[2-(4-Arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2H-benzimidazole-2-thiones: synthesis and pharmacological evaluation

Abstract

Eight new compounds with halogen atom introduced into the benzimi­dazo­le-2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihy­dro-2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure–affinity requirements, have been syn­thesized. All the new compounds were evaluated for the in vitro binding affinity at the dopa­mine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioas­says, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the bin­d­ing of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Diver­gently, the­se compounds were without significant affinities for the D1 DA receptors.

Keywords

• arylpiperazines
• benzimidazole-2-thiones
• dopamine receptors
• serotonin receptors