Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase γ

…, JP Shaw, K Roulin, F Burgat-Charvillon…

文献索引：Pomel, Vincent; Klicic, Jasna; Covini, David; Church, Dennis D.; Shaw, Jeffrey P.; Roulin, Karen; Burgat-Charvillon, Fabienne; Valognes, Delphine; Camps, Montserrat; Chabert, Christian; Gillieron, Corinne; Francon, Bernard; Perrin, Dominique; Leroy, Didier; Gretener, Denise; Nichols, Anthony; Vitte, Pierre Alain; Carboni, Susanna; Rommel, Christian; Schwarz, Matthias K.; Rueckle, Thomas Journal of Medicinal Chemistry, 2006 , vol. 49, # 13 p. 3857 - 3871

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被引用次数: 157

摘要

Class I phosphoinositide 3-kinases (PI3Ks), in particular PI3Kγ, have become attractive drug targets for inflammatory and autoimmune diseases. Here, we disclose a novel series of furan- 2-ylmethylene thiazolidinediones as selective, ATP-competitive PI3Kγ inhibitors. Structure- based design and X-ray crystallography of complexes formed by inhibitors bound to PI3Kγ identified key pharmacophore features for potency and selectivity. An acidic NH group on ...