Discovery and SAR of novel 4-thiazolyl-2-phenylaminopyrimidines as potent inhibitors of spleen tyrosine kinase (SYK)

A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar Ki’s against SYK and potent inhibition in mast cell degranulation assays.

Graphical abstractThe synthesis of potent novel SYK inhibitors such as 17 (Ki = 8 nm) is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide