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

A series of 1-substituted 2,4-dinitroimidazole analogues have been 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 (1) with a variety of oxiranes upon heating in absolute ethanol yielded the expected 1-substituted 2,4-dinitroimidazoles (2) and also resulted in the formation of a novel class of isomeric nitroimidazo[2,1-b]oxazoles 3 and 4) by intramolecular cyclization. The results of radiosensitizing activity of these agents against hypoxic Chinese hamster 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 (2d) was found to be the most effective radiosensitizer of this series.