Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors.

Abstract A series of PI3K-beta selective inhibitors, imidazo[1,2- a ]-pyrimidin-5(1 H )-ones, has been rationally designed based on the docking model of the more potent R enantiomer of TGX - 221 , identified by a chiral separation, in a PI3K-beta homology model. Synthesis and SAR of this novel chemotype are described. Several compounds in the series demonstrated potent growth inhibition in a PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage independent conditions.