4-amino metabolite

• 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: 4-amino metabolite
• 英文别名: 5-(Aziridin-1-yl)-4-amino-2-nitrobenzamide；4-amino-5-(aziridin-1-yl)-2-nitrobenzamide
• 化学式: C₉H₁₀N₄O₃
• 分子量: 222.203
• InChiKey: RQTUBPWOQMKLQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 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

• Therapeutic systems
  申请人：Enzacta R & D Limited

  公开号：US20030086933A1

  公开（公告）日：2003-05-08

  A compound comprising a target cell-specific portion and human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug, or a polynucleotide encoding said NQO2 or said variant or fragment or fusion or derivative. A recombinant polynucleotide comprising a target cell-specific promoter operably linked to a polynucleotide encoding human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug. The compounds and polynucleotides are useful in a method of treating a patient in conjunction with a suitable prodrug. A method of treating a human patient with a target cell to be destroyed wherein the target cell expresses NQO2 the method comprising administering to the patient a prodrug which is converted to a substantially cytotoxic drug by the action of NQO2 and nicotinamide riboside (reduced) (NRH) or an analogue thereof which can pass reducing equivalents to NQO2.

  该化合物包括一个靶细胞特异性部分和人类NAD（P）H：醌还原酶2（NQO2）或其变体或片段或融合物或衍生物，其对给定的前药具有与NQO2基本相同的活性，或者编码该NQO2或其变体或片段或融合物或衍生物的多核苷酸。一种重组多核苷酸，包括一个靶细胞特异性启动子与编码人类NAD（P）H：醌还原酶2（NQO2）或其变体或片段或融合物或衍生物的多核苷酸可操作地连接在一起，该NQO2或其变体或片段或融合物或衍生物对于给定的前药具有与NQO2基本相同的活性。这些化合物和多核苷酸在与合适的前药结合的方法中用于治疗患者。一种治疗表达NQO2的靶细胞的人类患者的方法，其中该方法包括向患者注射一种前药，该前药通过NQO2和烟酰胺核苷酸（还原）（NRH）或其类似物的作用被转化为基本上具有细胞毒性的药物。
• 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。
• Human quinone reductase 2 conjugates for ADEPT and GDEPT
  申请人：ENZACTA R & D LIMITED

  公开号：EP1468698A2

  公开（公告）日：2004-10-20

  A compound having formula I for use in medicine and, in particular, for the treatment of mammalian tumours. A compound comprising a target cell-specific portion and human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug, or a polynucleotide encoding said NQO2 or said variant or fragment or fusion or derivative. A recombinant polynucleotide comprising a target cell-specific promoter operably linked to a polynucleotide encoding human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug. The compounds and polynucleotides are useful in a method of treating a patient in conjunction with a suitable prodrug.

  一种具有式 I 的化合物，用于医药，特别是用于治疗哺乳动物肿瘤。 一种化合物，包括靶细胞特异性部分和人 NAD(P)H：醌还原酶 2 (NQO2)或其变体或片段或融合体或衍生物，其对给定原药的活性与 NQO2 基本相同；或编码所述 NQO2 或所述变体或片段或融合体或衍生物的多核苷酸。 一种重组多核苷酸，其包含与编码人NAD(P)H:醌还原酶2 (NQO2)或其变体或片段或融合体或衍生物的多核苷酸可操作地连接的靶细胞特异性启动子，该多核苷酸对给定原药具有与NQO2基本相同的活性。 这些化合物和多核苷酸在与合适的原药一起治疗患者的方法中是有用的。
• 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