Potent small molecule inhibitors of spleen tyrosine kinase (Syk)

Abstract A series of oxindoles demonstrating inhibition of the phosphorylation of biotinylated substrates of Syk and IgE/FceRI triggered basophil cell degranulation has been identified. A study of the SAR around sulfonamide 31 (IC 50 =5 nM, EC 50 =1400 nM) is discussed. The modest cellular activity representative of the sulfonamide series was overcome when the Polar Surface Area was lowered to 2 , leading to the identification of amide 32 (IC 50 =145 nM, EC 50 =100 nM).