Identification of pyrazolopyridine derivatives as novel spleen tyrosine kinase inhibitors.

Abstract

Inhibition of spleen tyrosine kinase (Syk) is a promising strategy for the treatment of various allergic and autoimmune disorders such as asthma, rheumatoid arthritis, and allergic rhinitis. Previously, a Syk inhibitor with novel indazole scaffold was discovered by structure-based virtual screening. Herein, the structure-activity relationship of the indazole Syk inhibitors was investigated. Several new inhibitors demonstrated potent activity against Syk. In particular, compound 18c showed good Syk inhibitory activity (IC50 = 1.2 µM), representing a good lead compound for further optimization.