[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase 尾 Inhibitors
文摘
A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3K尾. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R3) and back-pocket (R4) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey.
Keywords:
PI3K-尾 inhibitor; PTEN-null; phosphatidylinositol-3-kinase; pyrazolopyrimidine; structure鈭抋ctivity relationship