Nitro derivatives of bi- and tri-cyclic heterocycles as potential radiosensitizers

Article abstract of DOI:10.1016/0223-5234(89)90056-1

Two series of bicyclic compounds having a pyridinic and pyrrolic nitrogen atom in different rings have been synthesized as potential radiosensitizers of hypoxic mammalian cells.The compounds were obtained from 3-nitropyrrolo<2,3-b>pyridine by regioselective alkylation at the nitrogen atom in either the 5- or 6-membered rings.Partition coefficients, one electron reduction potentials, radiosensitization of Chinese hamster V79 cells and cytotoxicity were measured.Generally, the N-1 alkyl-substituted 3-nitropyrrolopyridines showed greater electron affinity than their N-7 alkyl-substituted analogues.All compounds were substantially less electron affinic than the 2-nitroimidazole, misonidazole.Consistent with this, misonidazole showed the most efficient sensitizing properties.None of the compounds synthesized here showed significantly lower toxicity than misonidazole.Consequently there is likely to be no therapeutic benefit from using these novel compounds as radiosensitizers. - 1-alkyl-3-nitro-1H-pyrrolo<2,3-b>pyridine preparation and radiosensitizer activity/7-alkyl-3-nitro-7H-pyrrolo<2,3-b>pyridine, preparation and redox properties/3-nitro-1H-pyrrolo<2,3-b>pyrazine/radiosensitization/cytotoxicity