Microwave expedited synthesis of 5-aminocamptothecin analogs: Inhibitors of hypoxia inducible factor HIF-1α

A series of 5-aminosubstituted camptothecin analogs were prepared from the corresponding 5-hydroxycamptothecin using microwave irradiation. The analogs were assayed for ability to inhibit the action of hypoxia inducible factors (HIF-1α and HIF-2α). The 5-fluoroethyl analog showed potent inhibitory activity and is now the focus of ongoing pathway analysis and potential as an antiproliferative agent.

Graphical abstractA series of 5-aminosubstituted camptothecin analogs were prepared using microwave accelerated synthesis. A fluoroethyl derivative showed superior inhibitory activity to camptothecin against the hypoxia inducible factor HIF-1α.Figure optionsDownload full-size imageDownload as PowerPoint slide