Synthesis and antitumor activity evaluation of 4,6-disubstituted quinazoline derivatives as novel PI3K inhibitors.

A series of 4,6-disubstituted quinazoline derivatives as potential PI3K inhibitors were designed and synthesized. All compounds exhibited significant anti-proliferative activities against HCT-116 and MCF-7 cell lines, and compounds A7, A9, and A11 displayed the most potent anti-proliferative activity against the HCT-116. Further PI3K inhibitory activity evaluation showed that compound A7 displayed high potency against PI3K enzymes. The in vivo anti-tumor study showed compound A7 can efficaciously inhibit tumor growth in a mice S-180 model. These results suggest that our designed compounds can serve as potent PI3K inhibitors and effective antitumor agents.