Potential Radiosensitizing Agents III: 2-Nitro-4-acetylimidazole analogs.

New analogs of 2-nitroimidazole have been synthesized in an effort to minimize the toxicity and increase selective sensitization of hypoxic mammalian cells toward lethal effects of ionizing radiation. 2-Nitro-4(5)-acetyl-5(4)-methylimidazole was synthesized from the corresponding 2-amino analog and then reacted with oxiranes to produce the corresponding 1-substituted 2-propanol and 3-methoxy-2-propanol derivatives. The biological results of radiosensitizing activity of these agents against Chinese hamster cells (V-79) indicated that the 3-methoxy-2-propanol derivative was a more effective radiosensitizer than misonidazole in vitro. Evaluation of the acute toxicity of these agents as determined by LD50 demonstrated no significant difference between these agents and misonidazole suggesting that the 3-methoxy-2-propanol analog may possess a therapeutic advantage over misonidazole.