Synthesis of Monomeric Derivatives To Probe Memoquin’s Bivalent Interactions

Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer’s disease. 2–4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. T...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2011-12, Vol.54 (24), p.8299-8304
Hauptverfasser:	Bolognesi, Maria Laura, Chiriano, GianPaolo, Bartolini, Manuela, Mancini, Francesca, Bottegoni, Giovanni, Maestri, Valentina, Czvitkovich, Stefan, Windisch, Manfred, Cavalli, Andrea, Minarini, Anna, Rosini, Michela, Tumiatti, Vincenzo, Andrisano, Vincenza, Melchiorre, Carlo
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetylcholinesterase - chemistry Alkanes - chemical synthesis Alkanes - chemistry Alkanes - pharmacology Amyloid beta-Peptides - chemistry Amyloid beta-Peptides - secretion Amyloid Precursor Protein Secretases - antagonists & inhibitors Animals Butyrylcholinesterase - chemistry Catalytic Domain Cell Survival - drug effects Chickens Cholinesterase Inhibitors - chemical synthesis Cholinesterase Inhibitors - chemistry Cholinesterase Inhibitors - pharmacology Ethylamines - chemical synthesis Ethylamines - chemistry Ethylamines - pharmacology Humans In Vitro Techniques Ligands Models, Molecular Molecular Conformation Neurons - cytology Neurons - drug effects Neurons - secretion Peptide Fragments - chemistry Peptide Fragments - secretion Protein Binding Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer’s disease. 2–4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm200691d