SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease

SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease

We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling a...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:ACS medicinal chemistry letters 2012-12, Vol.3 (12), p.1024-1028
Hauptverfasser: Wityak, John, Prime, Michael E, Brookfield, Frederick A, Courtney, Stephen M, Erfan, Sayeh, Johnsen, Siw, Johnson, Peter D, Li, Marie, Marston, Richard W, Reed, Laura, Vaidya, Darshan, Schaertl, Sabine, Pedret-Dunn, Anna, Beconi, Maria, Macdonald, Douglas, Muñoz-Sanjuan, Ignacio, Dominguez, Celia
Format: Artikel
Sprache:eng
Schlagworte:
Letter
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml300241m