Synthesis and structure–activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent β isoform selective phosphatidylinositol 3-kinase inhibitors

Abstract A series of 1,2,4-triazolo[1,5- a ]pyrimidin-7(3 H )-ones with excellent enzyme inhibition, improved isoform selectivity, and excellent inhibition of downstream phosphorylation of AKT has been identified. Several compounds in the series demonstrated potent (∼ 0.100 μM IC 50 ) growth inhibition in a PTEN deficient cancer cell line.