Synthesis and biological activity of a gemcitabine phosphoramidate prodrug.

Basic Information

ID: ALA1146216

Journal: J Med Chem

Title: Synthesis and biological activity of a gemcitabine phosphoramidate prodrug.

Authors: Wu W, Sigmond J, Peters GJ, Borch RF.

Abstract: A gemcitabine (2',2'-difluorodeoxycytidine, dFdC) phosphoramidate prodrug designed for the intracellular delivery of gemcitabine 5'-monophosphate was synthesized. The prodrug was about an order of magnitude less active than gemcitabine against wild-type cells, and the nucleoside transport inhibitor dipyridamole reduced prodrug activity. The prodrug was more active than gemcitabine against two deoxycytidine kinase-deficient cell lines. The results suggest that the prodrug is a potent growth inhibitor that can bypass dCK deficiency at higher drug concentrations.

CiteXplore: 17602464

DOI: 10.1021/jm070269u

Patent ID: