苯并咪唑类化合物的合成及辐射增敏作用

SYNTHESIS AND RADIOSENSITIZING ACTIVITY OF BENZIMIDAZOLES

为了寻找低毒和有效的辐射增敏剂,合成了苯并咪唑类化合物2-硝基苯并咪唑-1-甲酸乙酯,2-羟基苯并咪唑-1-甲酸乙酯及1-取代2-(3’-吡啶基)-5(6)-硝基苯并咪唑类化合物,并对小鼠Ehrlich腹水癌细胞进行了辐射增敏实验,初步结果证明所试化合物有不同程度的辐射增敏效果。

In search for effective radiosensitizer with low neurotoxicity, benzimidazole com-pounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl α-(2-nitrobenzimidazolyl-1)-formate (1) or ethyl α- (2-hydroxybenzimidazolyl-1)-formate (2), depend-ing upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,/2-epoxy-3-chloropropane gave acyclized compound which was confirmed to be benzimidazo(1,2b)-5′-chloromethyl-oxazolidine(3).In attempt to increase hydrophilicity, 1-substituted 2- (3′-pyridyl)-5-nitrobenzimidazoles wereprepared by reaction of 2-(3′-pyridyl)-5(6)-nitrobenzimidazole(4) with alkyl epoxides or ethylchloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich as-cites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizingactivity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be1.50, 1.52 and 1.65 respectively.