Discovery of new azaindole-based PI3Kα inhibitors: apoptotic and antiangiogenic effect on cancer cells.

Phosphatidylinositol-3-kinase alpha (PI3Kα) is an important target in cancer due to the deregulation of the PI3K/AKT signaling pathway in many tumors. In this study, we designed [3,5-d]-7-azaindole analogs as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3,5-positions of azaindole, we developed the SAR (Structure-activity relationship) and identified a series of potent PI3Kα inhibitors. Representative azaindole derivatives showed activity in a cellular proliferation and apoptosis assays. Moreover, B3 exhibited strong antiangiogenic effects on cancer cells.