5-(tert-butoxycarbonyl(chloro)methyl)-1-(2-(5-(tert-butoxycarbonyl(chloro)methyl)-4-nitro-1H-imidazol-1-yl)ethyl)-4-nitro-1H-imidazole | 1422986-73-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(tert-butoxycarbonyl(chloro)methyl)-1-(2-(5-(tert-butoxycarbonyl(chloro)methyl)-4-nitro-1H-imidazol-1-yl)ethyl)-4-nitro-1H-imidazole
• 英文别名: Tert-butyl 2-chloro-2-[3-[2-[5-[1-chloro-2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-4-nitroimidazol-1-yl]ethyl]-5-nitroimidazol-4-yl]acetate；tert-butyl 2-chloro-2-[3-[2-[5-[1-chloro-2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-4-nitroimidazol-1-yl]ethyl]-5-nitroimidazol-4-yl]acetate
• CAS: 1422986-73-9
• 化学式: C₂₀H₂₆Cl₂N₆O₈
• 分子量: 549.368
• InChiKey: WRVFPKQJVSBJRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  180
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-(tert-butoxycarbonyl(chloro)methyl)-1-(2-(5-(tert-butoxycarbonyl(chloro)methyl)-4-nitro-1H-imidazol-1-yl)ethyl)-4-nitro-1H-imidazole 在 溶剂黄146 作用下， 反应 4.0h， 以70%的产率得到5-(chloromethyl)-1-(2-(5-(chloromethyl)-4-nitro-1H-imidazol-1-yl)ethyl)-4-nitro-1H-imidazole
  参考文献：
  名称：

  ANTI-CANCER AGENTS

  摘要：

  本文描述了一些化合物，这些化合物可以被选择性地激活，以在肿瘤细胞中产生活性抗癌剂。还公开了包括这些化合物的药物组合物，以及使用这些化合物治疗癌症的方法。

  公开号：

  US20130045949A1
• 作为产物：
  描述：

  2,2-二氯乙酸叔丁酯 、 4-nitro-1-(2-(4-nitro-1H-imidazol-1-yl)ethyl)-1H-imidazole 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以30%的产率得到5-(tert-butoxycarbonyl(chloro)methyl)-1-(2-(5-(tert-butoxycarbonyl(chloro)methyl)-4-nitro-1H-imidazol-1-yl)ethyl)-4-nitro-1H-imidazole
  参考文献：
  名称：

  ANTI-CANCER AGENTS

  摘要：

  本文描述了一些化合物，这些化合物可以被选择性地激活，以在肿瘤细胞中产生活性抗癌剂。还公开了包括这些化合物的药物组合物，以及使用这些化合物治疗癌症的方法。

  公开号：

  US20130045949A1

文献信息

• UV-Induced DNA Interstrand Cross-Linking and Direct Strand Breaks from a New Type of Binitroimidazole Analogue
  作者：Yanyan Han、Wenbing Chen、Yunyan Kuang、Huabing Sun、Zhiqiang Wang、Xiaohua Peng

  DOI：10.1021/tx500522r

  日期：2015.5.18

  Four novel photoactivated binitroimidazole prodrugs were synthesized. These agents produced DNA interstrand cross-links (ICLs) and direct strand breaks (DSB) upon UV irradiation, whereas no or very few DNA ICLs and DSBs were observed without UV treatment. Although these four molecules (1-4) contain the same binitroimidazole moiety, they bear four different leaving groups, which resulted in their producing different yields of DNA damage. Compound 4, with nitrogen mustard as a leaving group, showed the highest ICL yield. Surprisingly, compounds 1-3, without any alkylating functional group, also induced DNA ICL formation, although they did so with lower yields, which suggested that the binitroimidazole moiety released from UV irradiation Of 1-3 is capable of cross-linking DNA. The DNA cross-linked products induced by these compounds were completely destroyed upon 1.0 M piperidine treatment at 90 degrees C (leading to cleavage at dG sites), which revealed that DNA cross-linking mainly occurred via alkylation of dGs. We proposed a possible mechanism by which alkylating agents were released from these compounds. HRMS and NMR analysis confirmed that free nitrogen mustards were generated by UV irradiation of 4. Suppression of DNA ICL and DSB formation by a radical trap, TEMPO, indicated the involvement of free radicals it, the photo reactions of 3 and 4 with DNA. On the basis of these data, We propose that UV irradiation of compounds 1-4 generated a binitroimidazole intermediate that cross-links DNA. The higher ICL yield observed with 4 resulted from the amine effector nitrogen mustard released from UV irradiation.