New non-hydroxamic ADAMTS-5 inhibitors based on the 1,2,4-triazole-3-thiol scaffold

In this Letter we describe the design, synthesis, screening, and optimization of a new family of ADAMTS-5 inhibitors. These inhibitors display an original 1,2,4-triazole-3-thiol scaffold as a putative zinc binding-group. In vitro results are rationalized by in silico docking of the compounds in ADAM...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (21), p.6213-6216
Hauptverfasser:	Maingot, Lucie, Leroux, Florence, Landry, Valérie, Dumont, Julie, Nagase, Hideaki, Villoutreix, Bruno, Sperandio, Olivier, Deprez-Poulain, Rebecca, Deprez, Benoit
Format:	Artikel
Sprache:	eng
Schlagworte:	1,2,4-Triazol-3-thiol ADAM Proteins - antagonists & inhibitors ADAMTS-5 ADAMTS5 Protein Binding Sites Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Computer Simulation Drug Evaluation, Preclinical Humans Indicators and Reagents Medical sciences Metalloprotease Models, Molecular Osteoarthritis - drug therapy Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Protein Binding Protein Conformation Structure-Activity Relationship Triazol-5-thiol Triazoles - chemical synthesis Triazoles - chemistry Triazoles - pharmacology X-Ray Diffraction
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	In this Letter we describe the design, synthesis, screening, and optimization of a new family of ADAMTS-5 inhibitors. These inhibitors display an original 1,2,4-triazole-3-thiol scaffold as a putative zinc binding-group. In vitro results are rationalized by in silico docking of the compounds in ADAMTS-5’s crystal structure.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.08.108