Design, synthesis and properties of several heterocyclic dopaminergic ligands.
Two series of non-catechol dopamine (DA) bioisosteres with the hydroxyl groups on the benzene ring replaced by N-H groups were synthesized using phenethylamine as a parent molecule. Compounds from the first series (1-9) contained a primary amine group, while those from the second one (10-19) had a N,N-di-propylamino group introduced into the side chain of the phenethylamine. The affinity and selectivity of these compounds for the D-1 and D-2 subtypes of the DA receptor were determined in competition binding assays using synaptosomal membranes from bovine caudate nuclei and [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) as radioligands. None of the 19 compounds examined expressed significant affinity for D-1 receptors, while compounds 15, 17 and 19, in this order of potency, strongly competed with [3H]spiperone binding to D-2 receptors under conditions that prevented radioligand binding to serotonin 5HT2 receptors. Varying affinities of the compounds examined for the DA receptors can be ascribed to different acidity of the N-H groups introduced at meta- and para-positions of the phenethylamine molecule.
Kostić
S
S
Institute for Chemistry, Technology and Metallurgy, Belgrade, Yugoslavia.
Soskić
V
V
Joksimović
J
J
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002417:Cattle; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000737:chemistry; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013134:Spiperone / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D006571:Heterocyclic Compounds; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D004298:Dopamine