A new series of 3-amidoquinoline derivatives were designed, synthesized and evaluated as PI3K/mTOR dual inhibitors. Among them, five compounds showed potent PI3Kα inhibitory activities (IC50 < 10 nM) and anti-proliferative activities (IC50 < 1 μM). The representative compound 15a can significantly inhibit other class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level, suggesting that 15a was a potent PI3K/mTOR dual inhibitor. Moreover, 15a displayed favorable pharmacokinetic properties in vivo.
