Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10587292 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
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 kinase selectivity.
Keywords
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Chemistry
Organic Chemistry
Authors
Bradley J. Newhouse, Steve Wenglowsky, Jonas Grina, Ellen R. Laird, Walter C. Voegtli, Li Ren, Kateri Ahrendt, Alex Buckmelter, Susan L. Gloor, Nathalie Klopfenstein, Joachim Rudolph, Zhaoyang Wen, Xianfeng Li, Bainian Feng,