Potential radiosensitizing agents. 2. Synthesis and biological activity of derivatives of dinitroimidazole with oxiranes.
Potential radiosensitizing agents. 2. Synthesis and biological activity of derivatives of dinitroimidazole with oxiranes.
复制标题
潜在的放射增敏剂。
DOI：
10.1021/jm00137a021
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发表时间：
1981
影响因子：
7.3
通讯作者：
K. Agrawal
中科院分区：
文献类型：
--
作者：
R. K. Sehgal;M. W. Webb;K. Agrawal
合成了一系列1-取代的2，4-二硝基咪唑类似物，并测试了它们选择性地使缺氧哺乳动物细胞对辐射致死效应增敏的放射增敏能力。2，4-（5）-二硝基咪唑（1）在无水乙醇中加热时与各种环氧乙烷反应，得到预期的1-取代2，4-二硝基咪唑（2），并通过分子内环化形成一类新的同分异构体硝基咪唑并[2，1-B]恶唑（3和4）。对缺氧的中国仓鼠细胞（V-79）的放射增敏活性结果表明，2，4-二硝基咪唑类化合物比硝基咪唑并[2，1-B]恶唑类化合物具有更好的放射增敏作用，提示分子中含有2-硝基官能团是必要的。1-（2-羟基-3-甲氧丙基）-2，4-二硝基咪唑（2d）是该系列中最有效的放射增敏剂。
A series of 1-substituted 2,4-dinitroimidazole analogues have been synthesized and tested for their radiosensitizing ability for selectively sensitizing hypoxic mammalian cells to the lethal effect of radiation. The reaction of 2,4-(5)-dinitroimidazole (1) with a variety of oxiranes upon heating in absolute ethanol yielded the expected 1-substituted 2,4-dinitroimidazoles (2) and also resulted in the formation of a novel class of isomeric nitroimidazo[2,1-b]oxazoles 3 and 4) by intramolecular cyclization. The results of radiosensitizing activity of these agents against hypoxic Chinese hamster cells (V-79) indicated that 2,4-dinitroimidazoles were better sensitizers than the nitroimidazo[2,1-b]oxazoles, suggesting the necessity of the 2-nitro function in the molecule. The 1-(2-hydroxy-3-methoxypropyl)-2,4-dinitroimidazole (2d) was found to be the most effective radiosensitizer of this series.