Discovery of Potent, Efficient, and Selective Inhibitors of Phosphoinositide 3-Kinase delta through a Deconstruction and Regrowth Approach

摘要

A deconstruction of previously reported phosphoinositide 3-kinase delta (PI3K delta) inhibitors and subsequent regrowth led to the identification of a privileged fragment for PI3K delta, which was exploited to deliver a potent, efficient, and selective lead series with a novel binding mode observed in the PI3K delta crystal structure.