3－硝基－1，2，4－三唑类乏氧细胞放射增敏剂的构效关系  

STRUCTURE-ACTIVITY RELATIONSHIPS FOR 3-NITRO-1,2,4- TRIAZOLES AS HYPOXIC TUMOR CELL RADIOSENSTIZER

作　　者：仉文升[1] 沈恂[1] 李五岭[1] 吴艳芬[1] 蔡松君 李心愿[1] 汤丽霞[1] 王丽佳[1] 李仁利[1] 

机构地区：[1]北京医科大学药学院,中国科学院生物物理研究所

出　　处：《药学学报》1994年第10期739-745,共7页Acta Pharmaceutica Sinica

摘　　要：为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂，设计并合成了一系列５－溴－，５－甲基－，和５－未取代的３－硝基－１，２，４－三唑－１－乙酰胺类化合物，用ＨｅＬａＳ３细胞进行了体外试验。结果表明５－溴取代衍生物的增敏作用强于相应的５－甲基－或５－未取代的硝基三唑衍生物，但是它们的毒性亦增大。修饰１位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中ＴＡ－１０１［２－（３－硝基－１－三唑基）乙酰胺］由于有高的增敏作用和低亲脂性，可能是一个有希望的放射增敏剂。In order to search for effective radiosensitizer of hypoxic cell with low toxicity,a series of 5-bromo-,5-methy1-,and 5-unsubstituted-3-nitro-1,2,4-triazole-1- acetamides were synthesized and tested in vitro with HeLa S3 cells.The radiosensitlzing activity of 5-bromo-derivatives are more potent than those of corresponding 5-methyl-or 5- unsubstituted-1,2,4-triazole derivatives,but the chronic aerobic cytotoxicities are increased.Modification of the N1-acetamide side chain can also change the radiosensitizing activity and the lipophilicity.Among all the tested nitrotriazole derivatives, TA-101[2-(3- nitro-1-triazolyl)acetamide],may be a potential radiosensitizer because of its higher sensitizing activity and much lower lipophilicity.

关 键 词：放射增敏剂 构效关系 三唑类化合物 

分 类 号：R979.9[医药卫生—药品]