title: N-Substituted-2-alkyl- and 2-arylnorapomorphines: novel, highly active D2 agonists.
abstract: Two synthesis routes have been elaborated for the preparation of novel N-substituted-2-alkyl- and 2-arylnorapomorphines. The first one utilizes the traditional methodology of N-substitution of morphinans before acid-catalyzed rearrangements into aporphinoids, while our new approach involves the N-substitution directly on the aporphine backbone. The aimed compounds were obtained in similar overall yields in different synthesis routes and were investigated with respect to their binding affinities and activities to dopamine D(2) and D(1) receptors. These studies revealed remarkable affinity and selectivity of some compounds for D(2) over D(1) receptor subtypes. Partial or full agonist properties were confirmed for all tested compounds.
authors.affiliation: Institute of Chemistry, University of Tartu, Tartu, Estonia.
authors.forename: Laura
authors.initials: L
authors.lastname: Herm
authors.forename: Sándor
authors.initials: S
authors.lastname: Berényi
authors.forename: Argo
authors.initials: A
authors.lastname: Vonk
authors.forename: Ago
authors.initials: A
authors.lastname: Rinken
authors.forename: Attila
authors.initials: A
authors.lastname: Sipos
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001058:Apomorphine