Design, synthesis, biological evaluation and docking studies of novel 2-substituted-4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as dual PI3Kα/mTOR inhibitors

Four series of 2-substituted-4-morpholino- 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives were synthesized and evaluated for their activity against PI3Kα and mTOR kinase and cancer cell lines. The most promising compound 11 showed good antitumor potency for A549, PC-3 and MCF-7 cell lines with IC50 values of 0.52 ± 0.10 μM, 1.41 ± 0.10 μM, and 4.82 ± 0.24 μM, and strong antitumor activities against PI3Kα/mTOR with IC50 values of 6.72 ± 0.30 μM and 0.94 ± 0.10 μM.208