Discovery of pyrazolo [1, 5-a] pyridines as p110α-selective PI3 kinase inhibitors

JD Kendall, PD O'Connor, AJ Marshall…

文献索引：Kendall, Jackie D.; O'Connor, Patrick D.; Marshall, Andrew J.; Frederick, Raphael; Marshall, Elaine S.; Lill, Claire L.; Lee, Woo-Jeong; Kolekar, Sharada; Chao, Mindy; Malik, Alisha; Yu, Shuqiao; Chaussade, Claire; Buchanan, Christina; Rewcastle, Gordon W.; Baguley, Bruce C.; Flanagan, Jack U.; Jamieson, Stephen M.F.; Denny, William A.; Shepherd, Peter R. Bioorganic and Medicinal Chemistry, 2012 , vol. 20, # 1 p. 69 - 85

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被引用次数: 16

摘要

We have made a novel series of pyrazolo [1, 5-a] pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110α isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo [1, 5-a] pyridine ring system, and found compound 5x to be a particularly potent example (p110α IC50 0.9 nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, ...