Potential Radiosensitizing Agents III: 2-Nitro-4-Acetylimidazole Analogs

Article abstract of DOI:10.1002/jps.2600711105

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 posess a therapeutic advantage over misonidazole.