Discovery of GlyT1 inhibitors with improved pharmacokinetic properties

Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is dis...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-03, Vol.19 (5), p.1492-1495
Hauptverfasser:	Wolkenberg, Scott E., Zhao, Zhijian, Wisnoski, David D., Leister, William H., O’Brien, Julie, Lemaire, Wei, Williams, David L., Jacobson, Marlene A., Sur, Cyrille, Kinney, Gene G., Pettibone, Doug J., Tiller, Philip R., Smith, Sheri, Gibson, Christopher, Ma, Bennett K., Polsky-Fisher, Stacey L., Lindsley, Craig W., Hartman, George D.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Cassette dosing Dogs Drug Discovery - methods Glycine - biosynthesis Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors Glycine Plasma Membrane Transport Proteins - metabolism GlyT1 Humans Mice Mice, Inbred DBA N-Methylaspartate - chemistry N-Methylaspartate - pharmacology NMDA pharmacokinetics Piperidines - administration & dosage Piperidines - chemical synthesis Piperidines - pharmacokinetics Rats Schizophrenia Substrate Specificity Sulfonamides - chemical synthesis
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is discussed.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2009.01.015