Potential radiosensitizing agent. 4. 2-Nitroimidazole nucleosides

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Abstract
A series of 2-nitroimidazole nucleoside analogs was synthesized as potential radiosensitizers in an effort to reduce neurotoxicity and increase therapeutic efficacy. The 2,3,4,6-tetra-O-acetyl-.beta.-D-glucopyranosyl and glucothiopyranosyl analogs of 2-nitroimidazole were synthesized by condensation in the presence of stannic chloride and mercuric cyanide. The deacetylation of these esters was carried out with sodium methoxide at 0.degree. C. Condensation of the trimethylsilyl derivative of 2-nitroimidazole with methyl 2-deoxy-2-chloro-4,7,8,9-tetra-O-acetyl-N-acetyl-.alpha.-D-neuraminate was achieved in the presence of mercuric bromide. These agents were tested for cytotoxicity and radiosensitization in vitro against Chinese hamster [lung fibroblast] (V-79) cells under oxic and hypoxic conditions. The thioglucose and sialic acid analogs were active radiosensitizers.