A novel selective benzoxazepin inhibitor of PI3Kδ has been discovered. Beginning from compound 3, an αPI3K inhibitor, we utilized structure-based drug design and computational analysis of dihedral torsion angles to optimize for PI3Kδ isoform potency and isoform selectivity. Further medicinal chemistry optimization of the series led to the identification of 24, a highly potent and selective inhibitor of PI3Kδ.

中文翻译：

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通过二面角控制选择性苯并a庚因PI3Kδ抑制剂的设计

已经发现了新型的PI3Kδ选择性苯并x庚因抑制剂。从化合物3（一种αPI3K抑制剂）开始，我们利用基于结构的药物设计和二面角扭转角的计算分析来优化PI3Kδ同工型效价和同工型选择性。该系列药物的进一步化学优化导致鉴定出24种PI3Kδ的高效抑制剂。