Synthesis and evaluation of N,N-di-n-propyl-5,6,7,8-tetrahydro-1 H-benz[f]benzimidazol-6-yl-amine and related congeners as dopaminergic ligands.
Four semirigid dopaminergic biosiosteres (N,N-di-n-propyl-5,6,7,8-tetrahydro-1 H-benz[f]benzimidazol-6-yl-amine [sequence: see text] and three related congeners) were synthesized and chemically characterized. The affinity and selectivity of these compounds for D-1 and D-2 classes of the dopamine receptor were determined in competition binding experiments using synaptosomal membranes of the bovine caudate nuclei and [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) as radioligands. None of the four compounds tested expressed significant affinity for D-1 receptors and all of them competed moderately with [3H]spiperone binding to D-2 receptors under conditions that prevented radioligand binding to serotonin 5HT2 receptors. Some aspects of structure affinity relationship for this class of dopaminergic ligands are discussed.
Dragović
D
D
Department of Chemistry, Faculty of Veterinary Medicine, University of Belgrade, Yugoslavia.
Soskić
V
V
Joksimović
J
J
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001552:Benzazepines; D001562:Benzimidazoles; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D008024:Ligands; C096965:N,N-di-n-propyl-5,6,7,8-tetrahydro-1H-benz(f)benzimidazol-6-ylamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D015081:2-Naphthylamine