Discovery of 6-benzamide Containing 4-phenylquinazoline Derivatives as Novel PI3Kδ Inhibitors

In the present study, a series of new 6-benzamide containing 4-phenylquinazoline derivatives were designed and synthesized as PI3Kδ inhibitors. The preliminary SAR for this series of compounds was established. PI3Kδ inhibitory assay showed that most of the synthesized compounds achieved significant activity against PI3Kδ. Compound 12h was the most potent PI3Kδ inhibitor, displaying an IC50 value of 17 nM. These results reveal that the 6-benzamide containing 4-phenylquinazoline is an encouraging chemical substructure, deserving further structural exploration to identify novel and highly potent PI3Kδ inhibitors.