(o- and p-Nitrobenzyloxycarbonyl)-5-fluorouracil derivatives as potential conjugated bioreductive alkylating agents
- 1 January 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 29 (1) , 84-89
- https://doi.org/10.1021/jm00151a014
Abstract
A series of (o- and p-nitrobenzyloxycarbonyl)-5-fluorouracil derivatives were synthesized by reacting o- or p-nitrobenzyl chloroformate with 5-fluorouracil in the presence of triethylamine in DMF or Me2SO. The reductive activation of these agents was hypothesized to generate a reactive method and 5-fluorouracil, two components that are capable of synergistic interaction through complementary inhibition. Measurement of the surviving fractions of EMT6 tumor cells treated with these agents in culture under conditions in hypoxia and aerobiosis resulted in equal cell kill regardless of the state of oxygenation. One of the synthesized agents, 3-(p-nitrobenzyloxycarbonyl)-5-fluorouracil (4), appeared to be superior to 5-fluorouracil in prolonging the survival time of mice bearing intraperitoneal implants of the P388 leukemia and Sarcoma 180.This publication has 4 references indexed in Scilit:
- 2- and 6-Methyl-1,4-naphthoquinone derivatives as potential bioreductive alkylating agentsJournal of Medicinal Chemistry, 1982
- CLASSIFICATION OF ANTI-NEOPLASTIC AGENTS BY THEIR SELECTIVE TOXICITIES TOWARD OXYGENATED AND HYPOXIC TUMOR-CELLS1981
- PREFERENTIAL ACTIVATION OF MITOMYCIN-C TO CYTO-TOXIC METABOLITES BY HYPOXIC TUMOR-CELLS1980
- Potential bioreductive alkylating agents. 7. Antitumor effects of phenyl-substituted 2-chloromethyl-3-phenyl-1,4-naphthoquinonesJournal of Medicinal Chemistry, 1976