Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M(1) positive allosteric modulators

Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M(1) positive allosteric modulators

A series of methoxynaphthalene amides were prepared and evaluated as alternatives to quinolizidinone amide M1 positive allosteric modulators. A methoxy group was optimal for M1 activity and addressed key P-gp issues present in the aforementioned quinolizidinone amide series.

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bioorganic & medicinal chemistry letters 2014-03, Vol.24 (5), p.1417-1420
Hauptverfasser: Kuduk, Scott D, Di Marco, Christina N, Saffold, Jonathan R, Ray, William J, Ma, Lei, Wittmann, Marion, Koeplinger, Kenneth A, Thompson, Charles D, Hartman, George D, Bilodeau, Mark T, Beshore, Douglas C
Format: Artikel
Sprache:eng
Schlagworte:
Allosteric Regulation
Amides - chemical synthesis
Amides - chemistry
Amides - metabolism
Animals
CHO Cells
Cricetinae
Cricetulus
Mice
Naphthalenes - chemistry
Protein Binding
Quinolizidines - chemistry
Receptor, Muscarinic M1 - chemistry
Receptor, Muscarinic M1 - metabolism
Structure-Activity Relationship
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:A series of methoxynaphthalene amides were prepared and evaluated as alternatives to quinolizidinone amide M1 positive allosteric modulators. A methoxy group was optimal for M1 activity and addressed key P-gp issues present in the aforementioned quinolizidinone amide series.
ISSN:1464-3405
DOI:10.1016/j.bmcl.2014.01.012