Piperidine-derived g-secretase modulators

This Letter details the SAR of a novel series of piperidine-derived g-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Ab42, increase Ab38 and have no effect on Ab40 levels. Furthermore, 10h demonstrated excellent pharm...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2010-02, Vol.20 (3), p.1306-1311
Hauptverfasser:	Hall, Adrian, Elliott, Richard L, Giblin, Gerard MP, Hussain, Ishrut, Musgrave, James, Naylor, Alan, Sasse, Rosemary, Smith, Beverley
Format:	Artikel
Sprache:	eng
Online-Zugang:	Volltext
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Zusammenfassung:	This Letter details the SAR of a novel series of piperidine-derived g-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Ab42, increase Ab38 and have no effect on Ab40 levels. Furthermore, 10h demonstrated excellent pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS penetration in the mouse.
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2009.08.072