Design, synthesis and qualitative structure–activity evaluations of novel hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives as anticancer agents

Polysubstituted hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives were synthesized and biologically evaluated as novel anticancer agents. These motifs were produced by five steps reaction sequence in which Achmatowicz oxidative cyclization, is the basic protocol for such synthesis. To understand the structure–activity relationships of the newly synthesized motifs, two traditional medicinal chemistry strategies namely, ring expansion and contraction, were followed in this article. These studies indicated that tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives are more selective for breast cancer cell line compared to other cell lines under investigations. Furthermore, it was found that hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one derivatives are potent anticancer agents compared to tetrahydropyrano[3,2-b]pyrrol-2(1H)-one analogs. These findings, however, form the foundation for further investigation in our continuing efforts to develop selective anticancer agents.

Polysubstituted hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives were synthesized and biologically evaluated as novel anticancer agents.Figure optionsDownload as PowerPoint slide