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

Journal Article · Fri May 01 04:00:00 EDT 1981 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00137a021· OSTI ID:5285031

Sehgal, R K; Webb, M W; Agrawal, K C

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.

• OSTI ID: 5285031
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 24:5; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
560121 -- Radiation Effects on Cells-- External Source-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AZOLES
BIOCHEMICAL REACTION KINETICS
CELL CULTURES
CHEMICAL PREPARATION
COMPARATIVE EVALUATIONS
DRUGS
EPOXIDES
EXTERNAL IRRADIATION
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IRRADIATION
KINETICS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
REACTION KINETICS
SYNTHESIS
VERTEBRATES