Design of Selective Benzoxazepin PI3Kδ Inhibitors Through Control of Dihedral Angles.

ABSTRACT: 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.

SUBMITTER: Safina BS 

PROVIDER: S-EPMC5601369 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature