Design and synthesis of novel 6-aryl substituted 4-anilinequinazoline derivatives as potential PI3Kδ inhibitors

In this study, a series of new 6-aryl substituted 4-anilinequinazolines was designed and synthesized as PI3K delta inhibitors based on our reported chemical structures. The preliminary structure-activity relationship (SAR) was established, and compounds 13h and 13k displayed most potent PI3K delta inhibitory activities with the IC50 values of 9.3 nM and 9.7 nM, respectively. Compound 13h demonstrated similar anti proliferative profiles to idelalisib against three human B cell lines. Three key hydrogen bonding interactions were found in the docking of 13h with PI3K delta enzyme. These results suggest that compound 13h possessed nanomolar PI3K delta inhibitory activity and distinctive chemical structure, deserving further structural optimization. (C) 2017 Elsevier Ltd. All rights reserved.