2-amino-5-(aziridin-1-yl)-4-nitrobenzamide | 61837-26-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-5-(aziridin-1-yl)-4-nitrobenzamide
• 英文别名: Benzamide, 2-amino-5-(1-aziridinyl)-4-nitro-
• CAS: 61837-26-1
• 化学式: C₉H₁₀N₄O₃
• 分子量: 222.203
• InChiKey: GMSKUYVZSLJSGF-UHFFFAOYSA-N

物化性质

• 沸点：
  441.0±45.0 °C(Predicted)
• 密度：
  1.572±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-(1-氮杂环丙基)-2,4-二硝基苯甲酰胺 在 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.5h， 生成 4-amino metabolite 、 2-amino-5-(aziridin-1-yl)-4-nitrobenzamide 、 5-(氮丙啶-1-基)-4-羟基氨基-2-硝基苯甲酰胺 、 5-(aziridin-1-yl)-2-hydroxylamino-4-nitrobenzamide
  参考文献：
  名称：

  通过修饰和固定化的硝基还原酶对酶促还原的前药CB1954的产物比率进行时变HPLC分析。

  摘要：

  定向酶前药疗法是一种化学疗法策略，利用前药激活酶在肿瘤部位激活前药，从而降低脱靶效应。与CB1954前药一起使用的最常研究的酶是来自大肠杆菌的NfnB硝基还原酶。文献指出，CB1954在2或4位上以1：1的比例被NfnB还原；在文献中已经观察到与该比率的偏差，但是没有进一步研究。基因修饰酶的动力学参数；评估了NfnB-his，NfnB-cys和AuNP-NfnB-cys，并使用HPLC分析来确定与CB1954反应时形成的羟胺产物比率。进行了与时间有关的HPLC研究，以评估该比率如何随时间变化。结果表明，由硝基还原酶还原CB1954形成的羟胺比率随时间变化，该比率的变化直接与反应动力学有关。因此，在给定的时间点使用HPLC测量的羟胺比率并不是真实地表明催化过程中硝基还原酶的偏好。这些结果质疑如何根据羟胺比率评估硝基还原酶，并且怀疑该现象也可能适用于其他酶/前药组合。

  DOI：

  10.1016/j.ejps.2018.11.001

文献信息

• Improvements relating to the control of neoplastic tissue growth
  申请人：Roberts, John J.

  公开号：EP0330432A1

  公开（公告）日：1989-08-30

  Compounds of the general formula: wherein R is H, an acyl group or a hydrocarbyl group containing up to 6 carbon atoms, have cytotoxic activity against several tumours. The 4-hydroxylamino compound can be obtained directly from the corresponding 2,4-dinitro compound by selective chemical reduction or by the action of a nitroreductase obtainable from Walker tumour cells. The 2,4-dinitro compound is substantially devoid of cytotoxic activity except in relation to Walker tumour cells and hence can act as a prodrug in regimes where a prodrug is localised in vivo in the regions of a tumour to be treated and is then activated to the cytotoxic 4-hydroxylamino compound under the influence of the enzyme.

  通式如下的化合物 其中 R 是 H、酰基或含有多达 6 个碳原子的烃基，对多种肿瘤具有细胞毒活性。4- 羟基氨基化合物可通过选择性化学还原法或可从沃克肿瘤细胞中获得的硝基还原酶的作用，直接从相应的 2,4-二硝基化合物中获得。2,4-二硝基化合物除对沃克肿瘤细胞外基本上没有细胞毒性活性，因此可以作为一种原药，在治疗肿瘤的过程中，原药在体内定位，然后在酶的作用下活化成具有细胞毒性的 4-羟基氨基化合物。
• An unusually cold active nitroreductase for prodrug activations
  作者：Ayhan Çelik、Gülden Yetiş

  DOI：10.1016/j.bmc.2012.04.004

  日期：2012.6

  A set of PCR primers based on the genome sequence were used to clone a gene encoding a hypothetical nitroreductases (named as Ssap-NtrB) from uropathogenic staphylococcus, Staphylococcus saprophyticus strain ATCC 15305, an oxygen insensitive flavoenzyme. Activity studies of the translation product revealed that the nitroreductase catalyses two electron reduction of a nitroaromatic drug of nitrofurazone (NFZ), cancer prodrugs of CB1954 and SN23862 at optimum temperature of 20 degrees C together with retaining its maximum activity considerably at 3 degrees C. The required electrons for such reduction could be supplied by either NADH or NADPH with a small preference for the latter. The gene was engineered for heterologous expression in Escherichia coli, and conditions were found in which the enzyme was produced in a mostly soluble form. The recombinant enzyme was purified to homogeneity and physical, spectral and catalytical properties were determined. The findings lead us to propose that Ssap-NtrB represents a novel nitro reductase with an unusual cold active property, which has not been described previously for prodrug activating enzymes of nitroreductases. (C) 2012 Elsevier Ltd. All rights reserved.
• IMPROVEMENTS RELATING TO THE CONTROL OF NEOPLASTIC TISSUE GROWTH
  申请人：Roberts, John J.

  公开号：EP0429454A1

  公开（公告）日：1991-06-05
• BACTERIAL NITROREDUCTASE FOR THE REDUCTION OF CB 1954 AND ANALOGUES THEREOF TO A CYTOTOXIC FORM
  申请人：Cancer Research Technology Limited

  公开号：EP0638123B1

  公开（公告）日：2006-12-27
• [EN] IMPROVEMENTS RELATING TO THE CONTROL OF NEOPLASTIC TISSUE GROWTH
  申请人：ROBERTS, John, J.

  公开号：WO1989007592A1

  公开（公告）日：1989-08-24

  (EN) Compounds of general formula (I), wherein R is H, an acyl group or a hydrocarbyl group containing up to 6 carbon atoms, have cytotoxic activity against several tumours. The 4-hydroxylamino compound can be obtained directly from the corresponding 2,4-dinitro compound by selective chemical reduction or by the action of a nitroreductase obtainable from Walker tumour cells. The 2,4-dinitro compound is substantially devoid of cytotoxic activity except in relation to Walker tumour cells and hence can act as a prodrug in regimes where a prodrug is localised $i(in vivo) in the regions of a tumour to be treated and is then activated to the cytotoxic 4-hydroxylamino compound under the influence of the enzyme.(FR) Les composés de la formule générale (I), dans laquelle R représente H, un groupe acyle ou un groupe hydrocarbyle contenant jusqu'à 6 atomes de carbone, ont une activité cytotoxique contre plusieurs tumeurs. On peut obtenir directement le composé 4-hydroxylamino à partir du composé 2,4-dinitro correspondant par réduction chimique sélective ou par l'action d'une nitroréductase que l'on peut obtenir à partir de cellules tumorales de Walker. Le composé 2,4-dinitro est sensiblement dépourvu d'activité cytotoxique excepté à l'égard des cellules tumorales de Walker, et donc il peut faire office de promédicament dans des régimes dans lesquels un promédicament est localisé $i(in vivo) dans les régions d'une tumeur à traiter, il est alors activé pour devenir le composé 4-hydroxylamino cytotoxique sous l'effet de l'enzyme.