Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3K <i>α</i> inhibitors

Abstract

Inhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3K<i>α</i> and a panel of PI3K<i>α</i>-addicted cancer cells. Among them, compound <b>35</b> was identified as a PI3K<i>α</i> inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed <b>35</b> induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable <i>in vitro</i> ADME properties. The design, synthesis, and SAR exploration of <b>35</b> are described within.