Potential radiosensitizing agents. Dinitroimidazoles

J Med Chem. 1979 May;22(5):583-6. doi: 10.1021/jm00191a025.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Escherichia coli / drug effects
  • Escherichia coli / radiation effects
  • Models, Molecular
  • Nitroimidazoles / chemical synthesis*
  • Nitroimidazoles / pharmacology
  • Oxygen / pharmacology
  • Radiation-Sensitizing Agents / chemical synthesis*
  • X-Ray Diffraction

Substances

  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • Oxygen