N,N-bis(2-chloroethyl)-N-methyl-N-[(1-methyl-4-nitro-5-imidazolyl)-methyl]ammonium chloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N-bis(2-chloroethyl)-N-methyl-N-[(1-methyl-4-nitro-5-imidazolyl)-methyl]ammonium chloride
• 英文别名: N,N-bis(2-chloroethyl)-N-methyl-N-[(1-methyl-4-nitro-5-imidazolyl)methyl]ammonium chloride；bis(2-chloroethyl)-methyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;chloride
• 化学式: C₁₀H₁₇Cl₂N₄O₂*Cl
• 分子量: 331.63
• InChiKey: FZGCLOUSZIVYHQ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.24
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-bis(2-chloroethyl)-N-methyl-N-[(1-methyl-4-nitro-5-imidazolyl)-methyl]ammonium chloride 在 叔丁醇 作用下， 以 水 为溶剂， 生成 Bis-(2-chloro-ethyl)-methyl-(3-methyl-5-nitro-3H-imidazol-4-ylmethyl)-ammonium
  参考文献：
  名称：

  Pulse Radiolysis Studies on the Fragmentation of Arylmethyl Quaternary Nitrogen Mustards by One-Electron Reduction in Aqueous Solution

  摘要：

  The radical species formed on the reaction of e(aq)(-) with a series of aryl compounds, all containing a N,N-bis(2-chloroethyl)-N-methylammoniomethyl substituent, have been studied in neutral aqueous solutions by pulse radiolysis using optical absorption spectraphotometry. The benzene, 1, and 4-methylsulfonylbenzene, 2, derivatives fragmented Immediately to yield different amounts of benzyl radicals, but the 2-nitrobenzene, 3, and 4-nitrobenzene, 4, derivatives were reduced to long-lived radical anions which decayed by bimolecular processes. These nitrobenzene derivatives differed from the corresponding benzyl halides in that they did not fragment to benzyl radicals. Similarly, no evidence was found for the formation of a benzyl-type radical from the radical anion of the 8-nitronaphthalene derivative, 5. However, benzyl-type radicals were produced upon intramolecular electron transfer from the initially formed radical anions of the 4-nitro-5-imidazole, 6, and the 5-nitro-2-pyrrole, 7, derivatives at rate constants of (8.0 +/- 1.0) x 10(3) and (1.0 +/- 0.1) x 10(4) s(-1) respectively; The latter heterocyclic analogues provide an approach for release of cytotoxic tertiary amines via enzymatic or radiolytic reduction in hypoxic regions of tumors.

  DOI：

  10.1021/jp972311a
• 作为产物：
  描述：

  N,N-bis(2-hydroxyethyl)-N-methyl-N-[(1-methyl-4-nitro-5-imidazolyl)methyl]ammonium chloride 在 氯化亚砜 作用下， 反应 72.0h， 以66%的产率得到N,N-bis(2-chloroethyl)-N-methyl-N-[(1-methyl-4-nitro-5-imidazolyl)-methyl]ammonium chloride
  参考文献：
  名称：

  缺氧选择性抗肿瘤药。16.作为烷基化剂甲乙胺的生物还原性前药的硝基芳基甲基季盐。

  摘要：

  氮芥子碱的硝基苄基季盐先前已报道为低氧选择性细胞毒素。在本文中，我们描述了一系列杂环类似物的合成和评估，包括吡咯，咪唑，噻吩和吡唑的例子，这些例子被选择来涵盖一系列单电子还原电势（从-277至-511 mV）和取代模式。所有季盐化合物在体外的毒性均比甲乙胺低，并且在低氧条件下的毒性都比有氧条件下的毒性更高，尽管该系列中的差异差异很大。最有希望的类似物咪唑2在低氧的RIF-1细胞中表现出选择性的DNA交联，并且在体内与放射线或顺铂联合具有活性。但是，2在体内也产生了无法预测的毒性，

  DOI：

  10.1021/jm010202l

文献信息

• Radiation-activated cytotoxin therapy
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP1225169A1

  公开（公告）日：2002-07-24

  A method of treating neoplastic disease which comprises the steps of: (a) administering to a patient in need of such treatment an effective amount of a radiation-activated cytotoxin prodrug (RACP) which has low toxicity, which can be reduced by reducing agents generated by the radiolysis of water (the equated electron and/or the hydrogen radical) and which, upon reduction, releases a sufficient amount of an effector of sufficient cytotoxic potency to kill tumour cells; and (b) irradiating said tumour cells to reduce the prodrug which is present at the locus of said tumour cells to release said cytotoxic effector. In preferred embodiments, the RACP is of formula (I), (VI), (VII) or (VIII).

  一种治疗肿瘤性疾病的方法，包括以下步骤 (a) 给需要这种治疗的病人服用有效量的辐射活化细胞毒素原药(RACP)，该原药毒性低，可被水的辐射分解产生的还原剂(等价电子和/或氢自由基)还原，还原后释放出足够量的具有足够细胞毒性效力的效应物，以杀死肿瘤细胞；以及 (b) 对所述肿瘤细胞进行辐照，以还原存在于所述肿瘤细胞部位的原药，从而释放所述细胞毒性效应物。 在优选的实施方案中，RACP 是式 (I)、(VI)、(VII) 或 (VIII)。
• NITROBENZYL MUSTARD QUATERNARY SALTS AND THEIR USE AS HYPOXIA-SELECTIVE CYTOTOXIC AGENTS
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP0700376A1

  公开（公告）日：1996-03-13
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  公开号：EP0700376A4

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• US5691371A
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  公开号：US5691371A

  公开（公告）日：1997-11-25
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  公开（公告）日：1999-02-16