Potential radiosensitizing agents. 6. 2-Nitroimidazole nucleosides: arabinofuranosyl and hexopyranosyl analogues

Journal Article · Sat Jan 01 04:00:00 EST 1983 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00355a005· OSTI ID:5815885

Sakaguchi, M; Larroquette, C A; Agrawal, K C

New 2-nitroimidazole nucleosides have been synthesized as radiosensitizers of hypoxic mammalian cells in an attempt to reduce the neurotoxicity and to increase the therapeutic efficacy of this class of agents. The trimethylsilyl derivative of 2-nitroimidazole was condensed with 1-bromo-2,3,5-tri-O-benzoylarabinofuranose in the presence of mercuric cyanide to yield anomeric isomers of arabinofuranosides, which were separated by preparative thin-layer chromatography. Reaction of 2-deoxy-1,3,4,6-tetra-O-acetyl-D-glucose or 3,4,6-tri-O-acetyl-D-glucal with 2-nitroimidazole in the presence of an acid catalyst produced alpha and beta isomers of 2',3'-dideoxy-D-erythro-hex-2'-enopyranosides and an isomeric 3-substituted 1,2,3-trideoxy-D-erythro-hex-1-enopyranose. Hydrolysis of the esters was accomplished with sodium methoxide in methanol at 0 degrees C. The radiosensitizing efficacy of these agents was determined against Chinese hamster (V-79) cells in vitro. The 1-(2',3'-dideoxy-alpha-D-erythro-hex-2'-enopyranosyl)-2-nitroimidazole was the most active agent of this series and was found to be superior to misonidazole as a radiosensitizer.

• Research Organization: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana
• OSTI ID: 5815885
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 26:1; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
AZOLES
CHEMICAL PREPARATION
CHO CELLS
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MISONIDAZOLE
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RIBOSIDES
SYNTHESIS