Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents

► A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidines were synthesized. ► The relative stereochemistry of target compounds were confirmed by NOESY NMR spectra. ► Most of the synthesized compounds showed significant to moderate cytotoxic activity. ► Compound 15f was 1.7- to 66.5-folds more active than GDC-0941 against three cell lines. ► 3D-QSAR analysis employed by CoMFA and CoMSIA model on H460 cell line was investigated.