Design, synthesis, and structure–activity relationship of novel orally efficacious pyrazole/sulfonamide based dihydroquinoline γ-secretase inhibitors

In this Letter, we report our strategy to design potent and metabolically stable γ-secretase inhibitors that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose. In this Letter, we report our strategy to design potent and metabolically stable γ-secretase inhibitor...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-09, Vol.19 (17), p.4920-4923
Hauptverfasser:	Truong, Anh P., Aubele, Danielle L., Probst, Gary D., Neitzel, Martin L., Semko, Chris M., Bowers, Simeon, Dressen, Darren, Hom, Roy K., Konradi, Andrei W., Sham, Hing L., Garofalo, Albert W., Keim, Pamela S., Wu, Jing, Dappen, Michael S., Wong, Karina, Goldbach, Erich, Quinn, Kevin P., Sauer, John-Michael, Brigham, Elizabeth F., Wallace, William, Nguyen, Lan, Hemphill, Susanna S., Bova, Michael P., Basi, Guriqbal
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Alzheimer’s disease Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism Animals Drug Design Mice Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Pyrazoles - chemistry Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacology Structure-Activity Relationship Sulfonamides - chemistry γ-Secretase inhibitors
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Zusammenfassung:	In this Letter, we report our strategy to design potent and metabolically stable γ-secretase inhibitors that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose. In this Letter, we report our strategy to design potent and metabolically stable γ-secretase inhibitors that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2009.07.092