Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: Synthesis, SAR, PK/PD and activity in a preclinical model of rheumatoid arthritis

The synthesis, structure–activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be efficacious in a murine model for rheumatoid arthritis. The synthesis, structure–activity relationships (SAR) and biological e...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (1), p.383-386
Hauptverfasser:	Dyckman, Alaric J., Langevine, Charles M., Quesnelle, Claude, Kempson, James, Guo, Junqing, Gill, Patrice, Spergel, Steven H., Watterson, Scott H., Li, Tianle, Nirschl, David S., Gillooly, Kathleen M., Pattoli, Mark A., McIntyre, Kim W., Chen, Laishun, McKinnon, Murray, Dodd, John H., Barrish, Joel C., Burke, James R., Pitts, William J.
Format:	Artikel
Sprache:	eng
Schlagworte:	animal models Animals Arthritis, Rheumatoid - drug therapy Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Disease Models, Animal Dogs Drug Evaluation, Preclinical Female I-kappa B Kinase - antagonists & inhibitors I-kappa B Kinase - metabolism IKK IKK2 IKKβ Imidazoles - chemistry Medical sciences Mice Mice, Inbred BALB C NF-κB Pharmacology. Drug treatments Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Protein Kinase Inhibitors - therapeutic use pyridines Pyridines - chemistry Pyridines - pharmacokinetics Pyridines - therapeutic use Rats rheumatoid arthritis Structure-Activity Relationship structure-activity relationships Thiazoles - chemistry
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The synthesis, structure–activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be efficacious in a murine model for rheumatoid arthritis. The synthesis, structure–activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be orally efficacious in a murine model of rheumatoid arthritis.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.10.133