title: Potential radiosensitizing agents. 6. 2-Nitroimidazole nucleosides: arabinofuranosyl and hexopyranosyl analogues.
abstract: New 2-nitroimidazole nucleosides have been synthesized as radiosensitizers of hypoxic mammalian cells in an attempt to reduce the neurotoxicity and to increase the therapeutic efficacy of this class of agents. The trimethylsilyl derivative of 2-nitroimidazole was condensed with 1-bromo-2,3,5-tri-O-benzoylarabinofuranose in the presence of mercuric cyanide to yield anomeric isomers of arabinofuranosides, which were separated by preparative thin-layer chromatography. Reaction of 2-deoxy-1,3,4,6-tetra-O-acetyl-D-glucose or 3,4,6-tri-O-acetyl-D-glucal with 2-nitroimidazole in the presence of an acid catalyst produced alpha and beta isomers of 2',3'-dideoxy-D-erythro-hex-2'-enopyranosides and an isomeric 3-substituted 1,2,3-trideoxy-D-erythro-hex-1-enopyranose. Hydrolysis of the esters was accomplished with sodium methoxide in methanol at 0 degrees C. The radiosensitizing efficacy of these agents was determined against Chinese hamster (V-79) cells in vitro. The 1-(2',3'-dideoxy-alpha-D-erythro-hex-2'-enopyranosyl)-2-nitroimidazole was the most active agent of this series and was found to be superior to misonidazole as a radiosensitizer.
mesh_terms: D000818:Animals; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D003412:Cricetulus; D006601:Hexoses / Q000138:chemical synthesis* / Q000494:pharmacology; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009705:Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*
chemical_list: D001087:Arabinonucleosides; D006601:Hexoses; D009593:Nitroimidazoles; D009705:Nucleosides; D011838:Radiation-Sensitizing Agents