Discovery of a novel tricyclic 4H-thiazolo[5′,4′:4,5]pyrano[2,3-c]pyridine-2-amino scaffold and its application in a PI3Kα inhibitor with high PI3K isoform selectivity and potent cellular activity

A novel, previously undescribed 4H-thiazolo[5′,4′:4,5]pyrano[2,3-c]pyridine tricyclic scaffold has been discovered. The application of this novel chemotype leading to a potent and selective prototype PI3Kα inhibitor with favorable physicochemical and PK-properties is described.