Document Detail

Synthesis and dopamine receptor binding of sulfur-containing aporphines.
MedLine Citation:
PMID:  16290940     Owner:  NLM     Status:  MEDLINE    
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.
Miklós Tóth; Sándor Berényi; Csaba Csutorás; Nora S Kula; Kehong Zhang; Ross J Baldessarini; John L Neumeyer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-15
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  14     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-10     Completed Date:  2006-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1918-23     Citation Subset:  IM    
University of Debrecen, Department of Organic Chemistry, H-4010 PO Box 20, Debrecen, Hungary.
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MeSH Terms
Aporphines / chemical synthesis*,  chemistry*,  pharmacology
Brain / drug effects,  metabolism,  physiology
Drug Evaluation, Preclinical
Molecular Structure
Motor Activity / drug effects
Receptors, Dopamine / metabolism*
Sulfur / chemistry*,  pharmacology
Reg. No./Substance:
0/Aporphines; 0/Receptors, Dopamine; 478-57-9/aporphine; 7704-34-9/Sulfur

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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