| Synthesis and biological evaluation of (R)-N-(diarylmethylthio/sulfinyl)ethyl/propyl-piperidine-3-carboxylic acid hydrochlorides as novel GABA uptake inhibitors. | |
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MedLine Citation:
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PMID: 17517506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jiange Zhang; Pei Zhang; Xianbo Liu; Kai Fang; Guoqiang Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-04-10 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 17 ISSN: 0960-894X ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-18 Completed Date: 2007-09-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 3769-73 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China. jgzhang5500@hotmail.com <jgzhang5500@hotmail.com> |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Mice Models, Chemical Nipecotic Acids / chemistry, pharmacology Piperidines / chemical synthesis*, chemistry Structure-Activity Relationship Temperature gamma-Aminobutyric Acid / pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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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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