Discovery of N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamides as novel, selective and potent GlyT1 inhibitors

Employing an iterative analogue library approach, novel potent and selective glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine sulfonamide have been discovered. These inhibitors are devoid of time-dependent CYP inhibition activity and exhibit improved aqueous solubility...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-03, Vol.19 (5), p.1488-1491
Hauptverfasser:	Zhao, Zhijian, Leister, William H., O’Brien, Julie A., Lemaire, Wei, Williams, David L., Jacobson, Marlene A., Sur, Cyrille, Kinney, Gene G., Pettibone, Doug J., Tiller, Philip R., Smith, Sheri, Hartman, George D., Lindsley, Craig W., Wolkenberg, Scott E.
Format:	Artikel
Sprache:	eng
Schlagworte:	Benzamides - chemical synthesis Benzamides - pharmacology Drug Discovery - methods Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors Glycine Plasma Membrane Transport Proteins - metabolism GlyT1 Humans Inhibitor N-{[1-(Propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamides NMDA receptor Piperidines - chemical synthesis Piperidines - pharmacology Schizophrenia Solubility Sulfonamides - chemical synthesis Sulfonamides - pharmacology
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Beschreibung
Zusammenfassung:	Employing an iterative analogue library approach, novel potent and selective glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine sulfonamide have been discovered. These inhibitors are devoid of time-dependent CYP inhibition activity and exhibit improved aqueous solubility versus the corresponding 4-phenylpiperidine analogues.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2008.12.115