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Synthesis and biological activity of a gemcitabine phosphoramidate prodrug.

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.

SUBMITTER: Wu W

PROVIDER: S-EPMC2518329 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Synthesis and biological activity of a gemcitabine phosphoramidate prodrug.

Wu Weidong W Sigmond Jennifer J Peters Godefridus J GJ Borch Richard F RF

Journal of medicinal chemistry 20070629 15

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 inhib ...[more]

PMID: 17602464

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