Synthesis of N-n-propyl-N-(2-arylethyl)-5-(1H-benzimidazol-2-thione)ethylamines and related compounds as potential dopaminergic ligands

  • 1 August 1996
    • journal article
    • research article
    • Vol. 46  (8) , 741-746
Abstract
Twelve different N-n-propyl-N-(2-arylethyl)-5-(1H-benzimidazol-2-thione)-ethylamines and 12 related heterocyclic congeners were synthesized with the aim of creating new high affinity dopaminergic ligands. Upon thorough chemical analysis they were evaluated for their affinity towards the D-l and the D-2 dopamine receptors (DAR) by in vitro binding assay using synaptosomal membranes of the bovine caudate nuclei and [H-3]SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride) (D-1 selective) and [3H]spiperone (D-2 selective) as the radioligands. None of the synthesized compounds expressed affinity for the binding to the D-1 DAR. Compounds 11e, 11j, 111, 12b, 12d, 13a, 13d, 14a and 14d were also inactive competitors of [H-3]spiperone binding to the D-2 DAR. However, 1H-benzimidazol-2-thione derivatives 11k, 11h and 11f and 1,4-di-hydroquinoxalin-2,3-dione derivative 12c (in this rank order of potencies) acted as strong competitors of [H-3]spiperone binding to the D-2 receptors under conditions that prevented radioligand binding to serotonin 5HT(2) receptors. Relationship between the structure and affinities of the new ligands for the binding to the D-2 DAR as well as the demands of the receptor itself for the interaction with the new compounds are discussed.

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