| Development of an (S)-1-{2-[Tris(4-methoxyphenyl)methoxy]ethyl}piperidine-3-carboxylic acid [(S)-SNAP-5114] Carba Analogue Inhibitor for Murine γ-Aminobutyric Acid Transporter Type 4. | |
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MedLine Citation:
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PMID: 22544452 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A series of GABA uptake inhibitors related to (S)-1-{2-[tris(4-methoxyphenyl)methoxy]ethyl}piperidine-3-carboxylic acid [(S)-SNAP-5114], the most potent mGAT4 inhibitor known so far, were synthesized and biologically evaluated for their inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK-293 cell lines. New analogues were developed with potencies that are similar to or slightly higher than those of current mGAT4 inhibitors, but with distinctly improved chemical stability. (S)-Nipecotic acid derivatives possessing a 2-[1-(4-methoxy-2-methylphenyl)-1,1-bis(4-methoxyphenyl)methoxy]ethyl (DDPM-859) or a 4,4,4-tris(4-methoxyphenyl)but-2-en-1-yl moiety (DDPM-1457) were found to exhibit pIC(50) values of 5.78 and 5.87, respectively. Thus, as mGAT4 inhibitors, these compounds compare well with (S)-SNAP-5114 (pIC(50) =5.71), but are far more stable than the latter. Moreover, DDPM-859 displays a more favorable subtype selectivity for mGAT4 versus mGAT3 than does (S)-SNAP-5114. |
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Authors:
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Jörg Pabel; Mark Faust; Cornelia Prehn; Babette Wörlein; Lars Allmendinger; Georg Höfner; Klaus T Wanner |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-27 |
Journal Detail:
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Title: ChemMedChem Volume: - ISSN: 1860-7187 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101259013 Medline TA: ChemMedChem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Department für Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 München (Germany). |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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