Potent small molecule inhibitors of spleen tyrosine kinase (Syk)

…, DJ Aldous, S Thurairatnam, K Smith, D Wheeler…

Index: Lai, Justine Y. Q.; Cox, Paul J.; Patel, Rajesh; Sadiq, Shazia; Aldous, David J.; Thurairatnam, Sukanthini; Smith, Keith; Wheeler, Darren; Jagpal, Savita; Parveen, Sofia; Fenton, Gary; Harrison, Trevor K. P.; McCarthy, Clive; Bamborough, Paul Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 18 p. 3111 - 3114

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Citation Number: 73

Abstract

A series of oxindoles demonstrating inhibition of the phosphorylation of biotinylated substrates of Syk and IgE/FcεRI 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 Å2, leading to the identification of amide 32 ( ...