Document Detail

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.
MedLine Citation:
PMID:  22544452     Owner:  NLM     Status:  Publisher    
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.
Jörg Pabel; Mark Faust; Cornelia Prehn; Babette Wörlein; Lars Allmendinger; Georg Höfner; Klaus T Wanner
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-27
Journal Detail:
Title:  ChemMedChem     Volume:  -     ISSN:  1860-7187     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101259013     Medline TA:  ChemMedChem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Department für Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 München (Germany).
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