PuSH - Publikationsserver des Helmholtz Zentrums München

Pabel, J.* ; Faust, M.* ; Prehn, C. ; Wörlein, B.* ; Allmendinger, L.* ; Höfner, G.* ; Wanner, K.T.*

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.

ChemMedChem 7, 1245-1255 (2012)
Verlagsversion Volltext DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 mGAT14 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 pIC50 values of 5.78 and 5.87, respectively. Thus, as mGAT4 inhibitors, these compounds compare well with (S)-SNAP-5114 (pIC50=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.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Biological Activity; Gaba; Gat; Inhibitors; Mgat1-4; GABA UPTAKE INHIBITORS; DERIVATIVES; DRUGS; TIAGABINE; TARGETS; BRAIN; GAT-3
ISSN (print) / ISBN 1860-7179
e-ISSN 1860-7187
Zeitschrift ChemMedChem
Quellenangaben Band: 7, Heft: 7, Seiten: 1245-1255 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed