Document Detail

Synthesis and biological evaluation of (R)-N-(diarylmethylthio/sulfinyl)ethyl/propyl-piperidine-3-carboxylic acid hydrochlorides as novel GABA uptake inhibitors.
MedLine Citation:
PMID:  17517506     Owner:  NLM     Status:  MEDLINE    
A series of new (R)-1-(2-diarylmethylthio/sulfinyl)ethyl-piperidine-3-carboxylic acid hydrochlorides 5a-d/6a-d and (R)-1-(3-diarylmethylthio)propyl-piperidine-3-carboxylic acid hydrochlorides 5'a-d were synthesized and evaluated as gamma-aminobutyric acid uptake inhibitors through cultured cell lines expressing mouse GAT1. Biological screening results demonstrated that the compounds 6a-d with diarylmethylsulfinyl ethyl side chain show more potent GAT1 inhibitory activities than 5a-d/5'a-d with diarylmethylthio ethyl/propyl moieties. Some of them, such as 6a, exhibited excellent inhibitions of [(3)H]-GABA uptake in cultured cells, which is 496-fold higher than (R)-nipecotic acid and 11.5 times less than tiagabine. The synthesis and structure-activity relationships are discussed.
Jiange Zhang; Pei Zhang; Xianbo Liu; Kai Fang; Guoqiang Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-10
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  17     ISSN:  0960-894X     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-18     Completed Date:  2007-09-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  3769-73     Citation Subset:  IM    
Department of Medicinal Chemistry, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China. <>
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MeSH Terms
Anticonvulsants / chemistry
Carboxylic Acids / chemical synthesis*,  chemistry
Chemistry, Pharmaceutical / methods*
Drug Design
GABA Antagonists / chemical synthesis*,  chemistry
GABA Plasma Membrane Transport Proteins / chemistry,  physiology*
Imidazoles / chemistry
Inhibitory Concentration 50
Models, Chemical
Nipecotic Acids / chemistry,  pharmacology
Piperidines / chemical synthesis*,  chemistry
Structure-Activity Relationship
gamma-Aminobutyric Acid / pharmacokinetics*
Reg. No./Substance:
0/Anticonvulsants; 0/Carboxylic Acids; 0/GABA Antagonists; 0/GABA Plasma Membrane Transport Proteins; 0/Imidazoles; 0/Nipecotic Acids; 0/Piperidines; 115103-54-3/tiagabine; 498-95-3/nipecotic acid; 56-12-2/gamma-Aminobutyric Acid

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

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