title: New 2-thioether-substituted apomorphines as potent and selective dopamine D₂ receptor agonists.
abstract: A set of novel apomorphine derivatives were synthesized with diversely functionalized side chains in the proximity of position 2 of the aporphine skeleton. Amino and/or carboxylic functions were introduced to this region of the backbone to test their pharmacological effects. During the synthesis of 2-(S-3-mercaptopropionic acid)-derivative a heteroring-fused congener was also isolated. The structural elucidation confirmed that the formation of this product was in accordance with our previous observations on the reaction of thebaine (2) with thiosalycilic acid. All the novel apomorphine congeners 4a-g were neuropharmacologically characterized to discover their dopaminergic profiles. Two derivatives were identified as D(2) full agonists equipotent with apomorphine (1) having significantly increased D(2)/D(1) selectivity ratios.
authors.affiliation: Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia.
authors.forename: Reet
authors.initials: R
authors.lastname: Reinart
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Gyulai
authors.forename: Sándor
authors.initials: S
authors.lastname: Berényi
authors.forename: Sándor
authors.initials: S
authors.lastname: Antus
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: D015097:3-Mercaptopropionic Acid / Q000737:chemistry; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D003412:Cricetulus; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D012459:Salicylates / Q000737:chemistry; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013797:Thebaine / Q000737:chemistry
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012459:Salicylates; D013438:Sulfhydryl Compounds; D013797:Thebaine; D015097:3-Mercaptopropionic Acid; C441201:thiosalicylic acid; D001058:Apomorphine