潜在的放射增敏剂。二硝基咪唑类。

Potential radiosensitizing agents. Dinitroimidazoles.

作者信息

Agrawal K C, Bears K B, Sehgal R K, Brown J N, Rist P E, Rupp W D

出版信息

J Med Chem. 1979 May;22(5):583-6. doi: 10.1021/jm00191a025.

Abstract

New compounds of the nitroimidazole series have been synthesized as radiosensitizers which selectively sensitize hypoxic cells to the lethal effect of radiation. The reaction of 2,4(5)-dinitroimidazole (2) with chloroethanol or hydrochloric acid yielded 4(5)-nitro-5(4)-chloroimidazole (3), which upon reaction with ethylene oxide yielded the 4-nitro-5-chloroimidazole-1-ethanol (6). Reaction of 2 with ethylene oxide resulted in a mixture of two compounds, the 2,4-dinitroimidazole-1-ethanol (4) and 2,3-dihydro-5-nitroimidazo[2,1-b]oxazole (5). The structure of the new heterocyclic compound 5 was confirmed by 1H NMR, mass spectrum, and X-ray crystallography. These agents were tested for their ability to sensitize hypoxic Escherichia coli cells to killing by ionizing radiation. Compound 4 was found to be the most active agent of this series of compounds.

摘要

已合成了硝基咪唑系列的新化合物作为放射增敏剂，其可选择性地使缺氧细胞对辐射的致死效应敏感。2,4(5)-二硝基咪唑(2)与氯乙醇或盐酸反应生成4(5)-硝基-5(4)-氯咪唑(3)，后者与环氧乙烷反应生成4-硝基-5-氯咪唑-1-乙醇(6)。2与环氧乙烷反应生成两种化合物的混合物，即2,4-二硝基咪唑-1-乙醇(4)和2,3-二氢-5-硝基咪唑并[2,1-b]恶唑(5)。通过1H NMR、质谱和X射线晶体学确定了新杂环化合物5的结构。测试了这些试剂使缺氧大肠杆菌细胞对电离辐射杀伤敏感的能力。发现化合物4是该系列化合物中活性最高的试剂。