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Synthesis and Dopaminergic Properties of 3‐ and 4‐Substituted 1‐{2‐[5‐(1 H ‐Benzimidazole‐2‐thione)]ethyl}piperidines and Related Compounds
Author(s) -
Dukic Sladjana,
KosticRajacic Sladjana,
Šoškic Vukic,
Joksimovic Jelena
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300107
Subject(s) - benzimidazole , chemistry , dopaminergic , receptor , stereochemistry , sch 23390 , dopamine receptor , dopamine , enantiomer , piperidine , ligand (biochemistry) , biochemistry , organic chemistry , biology , neuroscience
With an aim of creating new, high affinity dopaminergic ligands, six different 3‐ and 4‐substituted 1‐{2‐[5‐(1 H ‐benzimidazole‐2‐thione)]ethyl}piperidines and nine related heterocyclic congeners were synthesized and evaluated for in vitro binding affinity at D 1 and D 2 dopamine receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei were used as a source of the dopamine receptors. Only 4‐[ bis ‐(4‐fluorophenyl)methylene]‐piperidines, compounds 9e, 10d , and 11d , expressed moderate affinity for the D 1 receptors, while all other compounds were inactive competitors of [ 3 H]SCH 23390. Compounds 9c, 9d, 10c, 11a , and 11c were inactive in the D 2 receptor binding assay, as well. Derivatives of 4‐phenylpiperidine ( 9–11b ) and 3‐phenyl‐piperidine ( 10a ) expressed a moderate to low affinity for the D 2 receptors. However, racemic (±)‐1‐{2‐[5‐(1 H ‐benzimidazole‐2‐thione)]ethyl}‐3‐phenylpiperidine 9a and its enantiomer (+)‐ 9a behaved as selective, high affinity D 2 receptor ligands, the latter being some four times more active than the racemate.