Journal of Isotopes ›› 2018, Vol. 31 ›› Issue (4): 241-247.DOI: 10.7538/tws.2017.youxian.071

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Syntheses of Stable Isotopelabeled 1-(3-Methoxy-Phenyl)-[4-(4-Fluoro-2-Methoxy-D3-Phenylaminemethyl]-1h-[1,2,3]Triazole

XU Zhongjie1,2;TU Yahui1,2;ZHONG Jiaqi1,2;SUN Wen1,2;WANG Zhonghua3;WANG Haoran1,2;BAI Shaofei1,2;WU Fanhong3   

  1. 1.National Isotope Engineering Technology Research CenterShanghai Sub-Center, Shanghai Research Institute of Chemical Industry CO. LTD., Shanghai 200062, China; 2.Shanghai Engineering Research Center of Stable Isotope, Shanghai Research Institute of Chemical Industry CO. LTD., Shanghai 200062, China; 3.Shanghai Institute of Technology, Shanghai 201418, China
  • Online:2018-08-20 Published:2018-07-04



  1. 1.上海化工研究院有限公司 国家同位素工程技术研究中心 上海分中心,上海200062;2.上海化工研究院有限公司 上海稳定性同位素工程技术研究中心,上海200062;3.上海应用技术大学,上海201418


The research and development of effective anti-cancer drugs have been urgently needed. Molecular targeted drugs can be used to target tumor cells, which have good curative effect and little adverse reactions, and gradually become the development direction of anti-tumor drugs. As a molecular target drug Combretastatin A4 (CA4) can inhibit tubulin polymerization and splitso that researchers pay more and more attention to the modification of CA4 structure and similar things. The development of this area becomes one of the direction of anti-tumor drugs research hot spot. This article presented an efficient synthesis method of 1-(3-methoxy-phenyl)-[4-(4-Fluoro-2-methoxy-D3-phenylaminemethyl]-1H-[1,2,3]triazole with iodomethane-D3 as the common substrate, which was mainly obtained through methylation, reduction, substitution,azidation and cyclization reaction. The yields of 1-(3-methoxy-phenyl)-[4-(4-Fluoro-2-methoxy-D3-phenylaminemethyl]-1H-[1,2,3]triazole was 60.2% based on iodomethane-D3 consumed. The chemical purity of this product was 99.0% and deuterium isotopic enrichment of this product was 99.0%. The compound could be used in the field of antitumor drug because of a broad range of anticancer activity of it.

Key words: Combretastatin A4, stable isotope, anti-tumor, activity


分子靶向药物能够针对性地作用于肿瘤细胞,疗效良好,不良反应少,逐渐成为抗肿瘤药物的发展方向。作为分子靶向药物的考布他汀(Combretastatin A4, CA4)能够很好的抑制微管蛋白聚合和分裂,越来越重视对CA4结构的修饰以及类似物的开发,成为抗肿瘤新药研究的热点方向之一。本研究以廉价易得的碘甲烷-D3为原料,经过甲基化、硝基还原、炔基取代、叠氮化以及环化反应合成1-(3-甲氧基苯基)-[4-(4-氟-2-甲氧基-D3苯胺)甲基]-1,2,3-三氮唑。以消耗的碘甲烷-D3计,目标产物总收率为60.2%,化学纯度为99.0%,同位素丰度为99.0%。体外抗肿瘤实验表明,该化合物具有广谱的抗肿瘤活性,有望成为抗肿瘤药物。

关键词: 考布他汀, 稳定同位素, 抗肿瘤, 活性