Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors

An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (−)-1a (SCH 900229), a potent, PS1-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer’s disease. Specifically, 4-CF3 and 4-Br substituted arylsulfone a...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2013-02, Vol.23 (3), p.844-849
Hauptverfasser:	Wu, Wen-Lian, Asberom, Theodros, Bara, Thomas, Bennett, Chad, Burnett, Duane A., Clader, John, Domalski, Martin, Greenlee, William J., Josien, Hubert, McBriar, Mark, Rajagopalan, Murali, Vicarel, Monica, Xu, Ruo, Hyde, Lynn A., Del Vecchio, Robert A., Cohen-Williams, Mary E., Song, Lixin, Lee, Julie, Terracina, Giuseppe, Zhang, Qi, Nomeir, Amin, Parker, Eric M., Zhang, Lili
Format:	Artikel
Sprache:	eng
Schlagworte:	Alzheimer disease Alzheimer’s disease Amyloid Precursor Protein Secretases - antagonists & inhibitors Benzopyrans - chemical synthesis Benzopyrans - chemistry Benzopyrans - pharmacology Cyclization drugs Enzyme Activation - drug effects Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humans Inhibitory Concentration 50 Molecular Structure proteinase inhibitors proteinases Pyrans - chemical synthesis Pyrans - chemistry Pyrans - pharmacology Structure activity relationship structure-activity relationships Sulfone Sulfones - chemical synthesis Sulfones - chemistry Sulfones - pharmacology γ-Secretase inhibitor
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (−)-1a (SCH 900229), a potent, PS1-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer’s disease. Specifically, 4-CF3 and 4-Br substituted arylsulfone analogs, (−)-1b and (−)-1c, are equipotent to compound (−)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2012.11.047