Discovery of novel 2-piperidinol-3-(arylsulfonyl)quinoxalines as phosphoinositide 3-kinase α (PI3Kα) inhibitors

Article abstract of DOI:10.1016/j.bmc.2012.03.026

A series of novel 2-aliphatic cyclic amine-3-(arylsulfonyl)quinoxalines was synthesized based on the structural features of a previously identified lead, WR1. The 2-piperidinol-3-(arylsulfonyl)quinoxalines, which showed excellent antitumor activities against five human cell lines, with inhibitory activities ranging from 0.34 to 2.32 μM, proved to be a promising class of novel PI3Kα inhibitors. The most potent compound 10d (WR23) showed an inhibitory IC₅₀ value of 0.025 μM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.