Optimisation of ITK inhibitors through successive iterative design cycles

…, A Weber, J Jonveaux, F Schwoebel, M Stoeck…

文献索引：Herdemann, Matthias; Weber, Alexander; Jonveaux, Jerome; Schwoebel, Frank; Stoeck, Michael; Heit, Isabelle Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 6 p. 1852 - 1856

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被引用次数: 15

摘要

Based on a hit cluster of compounds inhibiting interleukin-2 inducible T-cell kinase (ITK) in the submicromolar range a series of ITK inhibitor libraries were synthesized. Through iterative design cycles including kinase crystal structure information, indolylindazole libraries were identified which showed low nanomolar activity in enzymatic and cellular assays. The potential of these novel lead series was confirmed through in vivo tests in an anti-CD3-IL2 ...