Discovery of Highly Isoform Selective Thiazolopiperidine Inhibitors of Phosphoinositide 3-Kinase 纬

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• 作者：Philip N. Collier ; David Messersmith ; Arnaud Le Tiran ; Upul K. Bandarage ; Christina Boucher ; Jon Come ; Kevin M. Cottrell ; Veronique Damagnez ; John D. Doran ; James P. Griffith ; Suvarna Khare-Pandit ; Elaine B. Krueger ; Mark W. Ledeboer ; Brian Ledford ; Yusheng Liao ; Sudipta Mahajan ; Cameron S. Moody ; Setu Roday ; Tiansheng Wang ; Jinwang Xu ; Alex M. Aronov
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：July 23, 2015
• 年：2015
• 卷：58
• 期：14
• 页码：5684-5688
• 全文大小：356K
• ISSN：1520-4804

文摘

A series of high affinity second-generation thiazolopiperidine inhibitors of PI3K纬 were designed based on some general observations around lipid kinase structure. Optimization of the alkylimidazole group led to inhibitors with higher levels of PI3K纬 selectivity. Additional insights into PI3K isoform selectivity related to sequence differences in a known distal hydrophobic pocket are also described.