Potential radiosensitizing agents. Dinitroimidazoles.
New compounds of the nitroimidazole series have been synthesized as radiosensitizers which selectively sensitize hypoxic cells to the lethal effect of radiation. The reaction of 2,4(5)-dinitroimidazole (2) with chloroethanol or hydrochloric acid yielded 4(5)-nitro-5(4)-chloroimidazole (3), which upon reaction with ethylene oxide yielded the 4-nitro-5-chloroimidazole-1-ethanol (6). Reaction of 2 with ethylene oxide resulted in a mixture of two compounds, the 2,4-dinitroimidazole-1-ethanol (4) and 2,3-dihydro-5-nitroimidazo[2,1-b]oxazole (5). The structure of the new heterocyclic compound 5 was confirmed by 1H NMR, mass spectrum, and X-ray crystallography. These agents were tested for their ability to sensitize hypoxic Escherichia coli cells to killing by ionizing radiation. Compound 4 was found to be the most active agent of this series of compounds.
D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D008958:Models, Molecular; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*; D014961:X-Ray Diffraction
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D010100:Oxygen