title: Potential radiosensitizing agents. 7. 4(5)-Iodo-5(4)-nitroimidazole derivatives.
abstract: A series of 4(5)-iodo-5(4)-nitro-1-substituted-imidazoles has been synthesized and tested for their ability to selectively radiosensitize hypoxic Chinese hamster cells (V-79) to the lethal effect of radiation. The reaction of 4(5)-iodo-5-(4)-nitroimidazole with 1,2-epoxy-3-methoxypropane and ethyl alpha-chloroacetate produced two isomeric products in each case, which were identified by their NMR spectra. The ethyl esters were further reacted with 3-picolylamine to produce corresponding amides. The 5-iodo-4-nitroimidazole-1-N-(3-picolyl)acetamide on further reaction with m-chloroperbenzoic acid produced the corresponding N-oxide. These compounds were generally more toxic to V-79 cells than the 2-nitroimidazole derivatives and were found to be more effective radiosensitizers in vitro. The 5-iodo-4-nitroimidazole derivatives were more efficient as sensitizers than the 4-iodo-5-nitroimidazole derivatives, and the sensitizing efficiency of this class of agents was found to have significant correlation with their partition coefficients.
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D000860:Hypoxia; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents