title: Synthesis and dopamine receptor binding of sulfur-containing aporphines.
abstract: We investigated acid-catalyzed rearrangement of thebaine 14 and its N-propyl analog 15 with methanesulfonic acid in the presence of the nucleophiles methanethiol and hydrogen sulfide. R(-)-2-methylthioapocodeine 16, R(-)-2-methylthioapomorphine 18, and their N-n-propyl analogs 17, 19 were obtained by rearrangement in the presence of methanethiol. However, with hydrogen sulfide, rearrangement of thebaine 14 and its N-n-propyl analog 15 produced sulfide-linked bis-aporphines 21-24 instead of expected R(-)-2-mercaptoapocodeines 12, 13 and R(-)-2-mercaptoapomorphines 10, 11. R(-)-2-Methylthio-N-n-propylnorapomorphine 19 had higher affinity (Ki = 3.7 nM) at D2 receptors in rat forebrain tissue than other novel 2-substituted sulfur-containing aporphines (Ki > or = 50 nM). Behavioral testing of the novel agents in rat indicated moderate locomotor arousal after systemic injection, and none after intragastric administration, indicating poor oral bioavailability.
authors.affiliation: University of Debrecen, Department of Organic Chemistry, H-4010 PO Box 20, Debrecen, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.forename: Sándor
authors.initials: S
authors.lastname: Berényi
authors.forename: Csaba
authors.initials: C
authors.lastname: Csutorás
authors.forename: Nora S
authors.initials: NS
authors.lastname: Kula
authors.forename: Kehong
authors.initials: K
authors.lastname: Zhang
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D008297:Male; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D013455:Sulfur / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001060:Aporphines; D011954:Receptors, Dopamine; C081279:aporphine; D013455:Sulfur