Potential radiosensitizing agents. 6. 2-Nitroimidazole nucleosides: arabinofuranosyl and hexopyranosyl analogues.
Potential radiosensitizing agents. 6. 2-Nitroimidazole nucleosides: arabinofuranosyl and hexopyranosyl analogues.
复制标题
潜在的放射增敏剂。
DOI：
10.1021/jm00355a005
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发表时间：
1983
影响因子：
7.3
通讯作者：
Agrawal,KC
中科院分区：
文献类型：
--
作者：
Sakaguchi,M;Larroquette,CA;Agrawal,KC
新的2-硝基咪唑核苷已被合成作为乏氧哺乳动物细胞的放射增敏剂，试图减少神经毒性并增加这类药物的治疗效果。2-硝基咪唑的三甲基硅衍生物与1-溴-2，3，5-三-O-苯甲酰基呋喃阿拉伯糖在汞氰化物存在下缩合，得到阿拉伯呋喃糖苷的异头异构体，其通过制备薄层色谱分离。2-脱氧-1，3，4，6-四-O-乙酰基-D-葡萄糖或3，4，6-三-O-乙酰基-D-葡萄糖醛与2-硝基咪唑在酸催化剂存在下反应，产生2，3 ′-二脱氧-D-赤式-己-2，3 ′-吡喃烯糖苷的α和β异构体和异构体3-取代的1，2，3-三脱氧-D-赤式-己-1-吡喃烯糖。酯的水解用甲醇钠在甲醇中于0 ℃完成.这些药物的放射增敏效果进行了测定对中国仓鼠（V-79）细胞在体外。1-（2 '，3'-双脱氧-aD-赤式-己-2 '-烯吡喃糖基）-2-硝基咪唑是这一系列化合物中活性最高的，其放射增敏作用上级米索硝唑。我们最近报道了一系列2，4-二硝基咪唑4 -6和2-乙酰基-4-硝基咪唑7的合成，
New 2-nitroimidazole nucleosides have been synthesized as radiosensitizers of hypoxic mammalian cells in an attempt to reduce theneurotoxicity and to increase the therapeutic efficacy of this class of agents. The trimethylsilyl derivative of 2-nitroimidazole was condensed with l-bromo-2, 3, 5-tri-0-benzoylarabinofuranose in the presence of mercuric cyanide to yield anomeric isomers of arabinofuranosides, which were separated by preparative thin-layer chromatography. Reaction of 2-deoxy-l, 3, 4, 6-tetra-0-acetyl-D-glucose or 3, 4, 6-tri-O-acetyl-D-glucal with 2-nitroimidazole in the presence of an acid catalyst produced a and ß isomers of 2,, 3'-dideoxy-D-erythro-hex-2,-enopyranosides and an isomeric 3-substituted 1, 2, 3-trideoxy-D-erythro-hex-l-enopyranose. Hydrolysis of the esters was accomplished with sodium methoxide in methanol at 0 C. The radiosensitizing efficacy of these agents was determined against Chinese hamster (V-79) cells in vitro. The l-(2', 3'-dideoxy-aD-erythro-hex-2,-enopyranosyl)-2-nitroimidazole was the most active agent of this series and was found to be superior to misonidazole as a radiosensitizer.A series of 2-nitroimidazole derivatives has been shown to selectively sensitize hypoxic cells, present in solid tu-mors, toward the lethal effect of ionizing radiation. 3 4567We have recently reported the synthesis of a series of 2, 4-dinitroimidazoles4-6 and 2-acetyl-4-nitroimidazoles7 in an