Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors.

Three series of novel thienopyrimidine derivatives -, -, and - were designed and synthesized, and their IC values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound showed moderate activity with IC values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respectively. The inhibitory activities of compounds and against PI3Kα and mTOR kinase were further evaluated. Compound exhibited PI3Kα kinase inhibitory activity with IC of 9.47 ± 0.63 µM. In addition, docking studies of compounds and were also investigated.