Potential radiosensitizing agents. 2. Synthesis and biological activity of derivatives of dinitroimidazole with oxiranes

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Abstract
A series of 1-substituted 2,4-dinitroimidazole analogs were synthesized and tested for their radiosensitizing ability for selectively sensitizing hypoxic mammalian cells to the lethal effect of radiation. The reaction of 2,4-(5)-dinitroimidazole with a variety of oxiranes upon heating in absolute ethanol yielded the expected 1-substituted 2,4-dinitroimidazoles and also resulted in the formation of a novel class of isomeric nitroimidazo[2,1-b]oxazoles by intramolecular cyclization. The results of radiosensitizing activity of these agents against hypoxic Chinese hamster lung cells (V-79) indicated that 2,4-dinitroimidazoles were better sensitizers than the nitroimidazo[2,1-b]oxazoles, suggesting the necessity of the 2-nitro function in the molecule. The 1-(2-hydroxy-3-methoxypropyl)2,4-dinitroimidazole was the most effective radiosensitizer of this series.