Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs

Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs

Guided by available X-ray crystal structure data on the serine protease thrombin, a series of pyridin-2-one derivatives were designed and synthesized having diverse functionality at the P(1) and P(3) sites. Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bioorganic & medicinal chemistry letters 2008-03, Vol.18 (6), p.1972-1976
Hauptverfasser: HANESSIAN, Stephen, SIMARD, Daniel, BAYRAKDARIAN, Malken, THERRIEN, Eric, NILSSON, Ingemar, FJELLSTRÖM, Ola
Format: Artikel
Sprache:eng
Schlagworte:
Amines - chemistry
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Crystallography, X-Ray
Drug Design
Humans
Medical sciences
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
Protein Binding
Protein Structure, Tertiary
Pyridones - chemical synthesis
Pyridones - chemistry
Pyridones - pharmacology
Structure-Activity Relationship
Sulfonamides - chemistry
Thrombin - antagonists & inhibitors
Thrombin - metabolism
Trypsin - chemistry
Trypsin - metabolism
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Guided by available X-ray crystal structure data on the serine protease thrombin, a series of pyridin-2-one derivatives were designed and synthesized having diverse functionality at the P(1) and P(3) sites. Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found for selected analogues.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2008.01.122