Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors.

Abstract We recently described several highly potent, triazine ( 1 ) and triazolopyrimidine ( 2 ) scaffold-based, dual PI3K/mTOR-inhibitors (e.g., 1 , PKI-587) that were efficacious in both in vitro and in vivo models. In order to further optimize these compounds we devised a novel series, the 2-oxatriazines, which also exhibited excellent potency and good metabolic stability. Some 2-oxatriazines showed promising in vivo biomarker suppression and induced apoptosis in the MDA-MB-361 breast cancer xenograft model.