Design, Synthesis, and Biological Evaluation of Imidazo[1,2-<i>a</i>]pyridine Derivatives as Novel PI3K/mTOR Dual Inhibitors
Yanan Yu, Yuqiao Han, Fupo Zhang, Zhenmei Gao, Tong Zhu, Suzhen Dong, Ming‐Liang Ma
Abstract
PI3K-Akt-mTOR signaling pathway has been validated as an effective targeting pathway for cancer therapy. However, no PI3K/mTOR dual inhibitor has been approved by the FDA yet. Therefore, it is still essential to discover a candidate with good efficacy and low toxicity. In our design, a series of imidazo[1,2-a]pyridine derivatives had been synthesized and subjected to activity assessment in vitro and in vivo. 15a was proved to be a potent PI3K/mTOR dual inhibitor with excellent kinase selectivity, modest plasma clearance, and acceptable oral bioavailability. Besides, 15a displayed significant inhibition of tumor growth in HCT116 and HT-29 xenografts without obvious effect on body weight.