6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as selective inhibitors of PI3Kα

Twenty eight 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4] oxazepine derivatives were synthesized and evaluated their biological activities as PI3K inhibitors. Biological evaluation against four human tumor cell lines revealed that most target compounds showed impressively better antiproliferative activities than that of LY294002. Among these compounds, compound 25 exhibited the most potent and selective activity for PI3K alpha, with the IC50 value of 0.016 mu M, an approximately 30-fold increase in comparison with LY294002, it also has an increased potency of approximately 11-fold for PI3K beta. It indicated the potential of developing 6,7-dihydrobenzo[f] benzo[4,5]imidazo[1,2-d][1,4] oxazepine derivatives as the new PI3K alpha selective inhibitors for tumor treatment. (C) 2015 Elsevier Ltd. All rights reserved.