Potent small molecule inhibitors of spleen tyrosine kinase (Syk)

A series of oxindoles demonstrating inhibition of the pbosphorylation of biotinylated substrates of Syk and IgE/FcepsilonRI triggered basophil cell degranulation has been identified. A study of the SAR around sulfonamide 31 (IC50=5 nM, EC50= 1400 nM) is discussed. The modest cellular activity representative of the sulfonamide series was overcome when the Polar surface Area was lowered to < 110 Angstrom(2), leading to the identification of amide 32 (IC50= 145 nM, EC50= 100 nM). (C) 2003 Published by Elsevier Ltd.