Imidazo [4, 5-b] pyridine inhibitors of B-Raf kinase

BJ Newhouse, S Wenglowsky, J Grina, ER Laird…

文献索引：Newhouse, Bradley J.; Wenglowsky, Steve; Grina, Jonas; Laird, Ellen R.; Voegtli, Walter C.; Ren, Li; Ahrendt, Kateri; Buckmelter, Alex; Gloor, Susan L.; Klopfenstein, Nathalie; Rudolph, Joachim; Wen, Zhaoyang; Li, Xianfeng; Feng, Bainian Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 21 p. 5896 - 5899

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被引用次数: 13

摘要

Abstract This Letter details the synthesis and evaluation of imidazo [4, 5-b] pyridines as inhibitors of B-Raf kinase. These compounds bind in a DFG-in, αC-helix out conformation of B-Raf, which is a binding mode associated with significant kinase selectivity. Structure– activity relationship studies involved optimization of the ATP-cleft binding region of these molecules, and led to compound 23, an inhibitor with excellent enzyme/cell potency, and ...