Gupta R P, Larroquette C A, Agrawal K C, Grodkowski J, Neta P
J Med Chem. 1985 Aug;28(8):987-91. doi: 10.1021/jm00146a003.
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.
已合成了一系列4(5)-碘-5(4)-硝基-1-取代咪唑，并测试了它们选择性地使缺氧的中国仓鼠细胞（V-79）对辐射的致死效应产生放射增敏的能力。4(5)-碘-5-(4)-硝基咪唑与1,2-环氧-3-甲氧基丙烷和α-氯乙酸乙酯的反应在每种情况下都产生了两种异构体产物，通过它们的核磁共振光谱进行了鉴定。乙酯进一步与3-吡啶甲胺反应生成相应的酰胺。5-碘-4-硝基咪唑-1-N-(3-吡啶基)乙酰胺与间氯过苯甲酸进一步反应生成相应的N-氧化物。这些化合物对V-79细胞的毒性通常比2-硝基咪唑衍生物更大，并且发现在体外是更有效的放射增敏剂。5-碘-4-硝基咪唑衍生物作为增敏剂比4-碘-5-硝基咪唑衍生物更有效，并且发现这类药剂的增敏效率与其分配系数有显著相关性。
