Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors

Indole substituted pyrazolylpyrimidine compound (16f) was identified as a potent and selective Syk inhibitor with good pharmacological profiles. [Display omitted] A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectiv...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2015-10, Vol.25 (20), p.4441-4446
Hauptverfasser:	Choi, Jang-Sik, Hwang, Hae-jun, Kim, Se-Won, Lee, Byung Il, Lee, Jaekyoo, Song, Ho-Juhn, Koh, Jong Sung, Kim, Jung-Ho, Lee, Phil Ho
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Crystallography, X-Ray Dogs Dose-Response Relationship, Drug Humans Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Intracellular Signaling Peptides and Proteins - metabolism Male Models, Molecular Molecular Structure Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - metabolism Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrazoles - pharmacology Pyrazolylpyrimidine Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Rats Rats, Sprague-Dawley Rheumatoid arthritis Spleen tyrosine kinase Structure-Activity Relationship Syk inhibitors Syk Kinase
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Indole substituted pyrazolylpyrimidine compound (16f) was identified as a potent and selective Syk inhibitor with good pharmacological profiles. [Display omitted] A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-α release assay.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2015.09.011