Discovery of 2-(5-(quinolin-6-yl)-1,3,4-oxadiazol-2-yl)acetamide derivatives as novel PI3Kα inhibitors via docking-based virtual screening.

PI3Kα is an attractive target for PIK3CA mutated malignant tumor and searching for lead compounds with novel scaffold is important for the development of PI3Kα inhibitors. Therefore, the strategy of docking-based virtual screening was performed to discovery potent inhibitors. The 4L2Y_A PI3Kα crystal structure was used as the model protein receptor due to its high docking reliability. After the multistep virtual screening protocol and biological evaluation, three hits were picked up and further similarity searching led to more potent 2-(5-(quinolin-6-yl)-1,3,4-oxadiazol-2-yl)acetamide derivatives ES-25 and ES-27. In addition, the primary SAR of these novel derivatives was discussed, which provide a basis for the further structural modification.