Design of potent inhibitors of human β-secretase. Part 2

We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of β-secretase that incorporate a variety of P 2 side chains that yield potent inhibitors with excellent cellular activity and good selectivity against Cathepsin-D. We describe an optimized series of acyclic hydr...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2007, Vol.17 (1), p.78-81
Hauptverfasser:	Freskos, John N., Fobian, Yvette M., Benson, Timothy E., Moon, Joseph B., Bienkowski, Michael J., Brown, David L., Emmons, Thomas L., Heintz, Robert, Laborde, Alice, McDonald, Joseph J., Mischke, Brent V., Molyneaux, John M., Mullins, Patrick B., Bryan Prince, D., Paddock, Donna J., Tomasselli, Alfredo G., Winterrowd, Greg
Format:	Artikel
Sprache:	eng
Schlagworte:	Alzheimer Disease - drug therapy Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - chemistry Carbamates - chemical synthesis Carbamates - chemistry Carbamates - pharmacology Cells, Cultured Drug Design Humans Hydroxyethylamine (HEA) isostere Molecular Structure Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Structure-Activity Relationship Sulfonamides - chemical synthesis Sulfonamides - chemistry Sulfonamides - pharmacology β-Secretase
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of β-secretase that incorporate a variety of P 2 side chains that yield potent inhibitors with excellent cellular activity and good selectivity against Cathepsin-D. We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of β-secretase that incorporates a variety of P 2 side chains that yield potent inhibitors with excellent cellular activity. A 2.2 Å crystal structure of compound 13 is shown.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2006.09.091