2,5-二氮杂环丙烷基-1,4-苯醌 | 526-62-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2,5-二氮杂环丙烷基-1,4-苯醌
• 英文名称: 2,5-bis(1-aziridinyl)-1,4-benzoquinone
• 英文别名: Ethylenimine quinone；2,5-bis(aziridin-1-yl)cyclohexa-2,5-diene-1,4-dione
• CAS: 526-62-5
• 化学式: C₁₀H₁₀N₂O₂
• 分子量: 190.202
• InChiKey: RCWJMKCTHJPXJV-UHFFFAOYSA-N

物化性质

• 沸点：
  325.7°C (rough estimate)
• 密度：
  1.2167 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R40
• 海关编码：
  2933990090
• 储存条件：
  库房应保持通风、低温和干燥，并与其他食品原料分开存放。

制备方法与用途

类别：有毒物品
毒性分级：高毒
急性毒性：腹腔-小鼠 LD50: 29.5 毫克/公斤
可燃性危险特性：可燃；燃烧产生有毒氮氧化物烟雾
储运特性：库房通风、低温干燥；与食品原料分开存放
灭火剂：干粉、泡沫、沙土、二氧化碳、雾状水

反应信息

• 作为反应物：
  描述：

  2,5-二氮杂环丙烷基-1,4-苯醌 在 sodium methylate 作用下， 以 氯仿 为溶剂， 反应 2.02h， 生成 5-methoxy-2-(2-methoxyethyl)amino-1,4-benzoquinone
  参考文献：
  名称：

  The stability of carboquone in alcohols. I. Kinetics and mechanisms of degradation of 2,5-bis(1-aziridinyl)-1,4-benzoquinone in alcohols.

  摘要：

  研究了2,5-双(1-氮杂环丙烷基)-1,4-苯醌(I)在醇类中的降解动力学和机制，并与之前在水溶液中获得的结果进行了比较。I在醇类中的降解遵循伪一级动力学，和在水溶液中的表现相同。在一系列醇中，降解速率与Kosower的Z值（溶剂极性的经验测量值）之间表现出良好的相关性。I在甲醇中的降解机制被仔细研究，因为I的降解速率相对较高，适合进行详细研究。在甲醇中观察到了五种化合物作为I的降解产物，I的降解过程看起来相当复杂。然而，I及这五种降解产物在质子丰富的甲醇和甲基化丰富的甲醇中的行为使我们能够推断出所有降解产物的化学结构：5-(1-氮杂环丙烷基)-2-(2-甲氧基乙基)氨基-1,4-苯醌，2,5-二(2-甲氧基乙基)氨基-1,4-苯醌，5-(1-氮杂环丙烷基)-2-甲氧基-1,4-苯醌，2,5-二甲氧基-1,4-苯醌和5-甲氧基-2-(2-甲氧基乙基)氨基-1,4-苯醌。它们的行为还清楚表明，I在甲醇中通过两种机制的组合进行降解：环氮杂烯的甲醇解作用，生成甲氧基乙基氨基，和环氮杂烯被甲氧基替代。因此，I在甲醇中的降解机制与在水溶液中的基本相同。

  DOI：

  10.1248/cpb.33.2983
• 作为产物：
  描述：

  甲氧苯醌 在 甲醇 作用下， 生成 2,5-二氮杂环丙烷基-1,4-苯醌
  参考文献：
  名称：

  Gauss, Chemische Berichte, 1958, vol. 91, p. 2216,2222

  摘要：

  DOI：

文献信息

• [EN] QUINONE COMPOUNDS AND THEIR USES FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS DE QUINONE ET LEURS UTILISATIONS POUR LE TRAITEMENT DE CANCER
  申请人：UNIV SALFORD

  公开号：WO2014020012A1

  公开（公告）日：2014-02-06

  Quinone Compounds and Their Uses for the Treatment of Cancer Quinone compounds having useful therapeutic activity such as anticancer activity, and compositions comprising such compounds, are described. The use of such compounds and compositions in the treatment of cancer is also described.

  醌化合物及其在癌症治疗中的用途 醌化合物具有有用的治疗活性，如抗癌活性，并描述了包含这些化合物的组合物。还描述了这些化合物和组合物在癌症治疗中的应用。
• Quinone Compounds And Their Uses For The Treatment of Cancer
  申请人：Onco-NX Limited

  公开号：US20150210639A1

  公开（公告）日：2015-07-30

  Quinone Compounds and Their Uses for the Treatment of Cancer Quinone compounds having useful therapeutic activity such as anticancer activity, and compositions comprising such compounds, are described. The use of such compounds and compositions in the treatment of cancer is also described.

  醌化合物及其在癌症治疗中的用途 醌化合物具有有用的治疗活性，如抗癌活性，并描述了包含这些化合物的组合物。还描述了这些化合物和组合物在癌症治疗中的应用。
• Über 2,5-Bisäthylenimino-hydrochinon, eine carcinostatisch wirksame Verbindung
  作者：A. Marxer

  DOI：10.1002/hlca.19550380620

  日期：——

  In the synthesis of 2,5-bis-ethylenimino-benzoquinone from benzoquinone and ethylenimine we isolated as the main product in addition to the desired quinone a white insoluble compound: the internal salt of 2,5-bis-ethylenimino-hydroquinone. We believe this product to represent a new type of compound, since from the series of aminophenols no internal salt seems to have been described. Thus amongst other

  在由苯醌和亚乙基亚胺合成2，5-双亚乙基氨基-苯醌的过程中，除所需的醌外，我们还分离出白色不溶性化合物作为主要产物：2,5-双亚乙基氨基-氢醌的内盐。我们认为该产品代表了一种新型的化合物，因为从一系列氨基酚类化合物来看，似乎没有描述内部盐。因此，在其他胺中，三甲基亚胺，吡咯烷，二甲胺给出了预期的氨基醌；单独使用哌啶时，会形成大量的双哌啶子基对苯二酚，后者不是内部盐。萘醌与亚乙基亚胺反应，得到醌衍生物。对于C，C-二甲基亚乙基亚胺，也已分离出二取代的醌，而C-甲基亚乙基亚胺类似于亚乙基亚胺本身，
• The stability of carboquone in aqueous solution. I. Kinetics and mechanisms of degradation of 2,5-diethylenimino-1,4-benzoquinone in aqueous solution.
  作者：AKIRA KUSAI、SEIJI TANAKA、SEIGO UEDA

  DOI：10.1248/cpb.29.3671

  日期：——

  The kinetics and mechanisms of the degradation of 2, 5-diethylenimino-1, 4-benzoquinone (EB) in aqueous solution were investigated as a function of pH (4-11), temperature (20-50°C), buffer concentration (0.01-0.1M) and ionic strength (0.1-0.5) by means of high pressure liquid chromatography. The reaction followed pseudo first-order kinetics. The pH-rate profile showed slopes of -1 at pH below 7.5 and +1 at pH over 7.5. Thus, the degradation of EB is subjected to specific acid-base catalysis. No effect of buffer concentration on the degradation rate of EB was apparent in the range of pH 4-11, though some effect of ionic strength on it was observed below pH 7. The apparent activation energies for the degradation of EB at pH 4 or 5 and pH 10 or 11 were 14 and 19 kcal/mol, respectively. In the range of pH 4-6, EB was degraded to 2, 5-diethanolamino-1, 4-benzoquinone with sequential hydrolytic cleavage of two ethylenimine rings. In the range of pH 10-11, EB was degraded to 2, 5-dihydroxy-1, 4-benzoquinone with sequential substitution of the two ethylenimine rings by hydroxyl ion (radical). In the range of pH 7-9, EB was degraded to 2, 5-diethanolamino-1, 4-benzoquinone, 2, 5-dihydroxy-1, 4-benzoquinone and 2-ethanol-amino-5-hydroxy-1, 4-benzoquinone by the two mechanisms described above.

  在不同pH（4-11）、温度（20-50°C）、缓冲液浓度（0.01-0.1M）和离子强度（0.1-0.5）条件下，采用高压液相色谱法研究了2, 5-二乙烯亚胺-1, 4-苯醌（EB）在水溶液中的降解动力学和机制。反应遵循伪一级动力学。pH-速率曲线显示，在pH低于7.5时斜率为-1，而在pH高于7.5时斜率为+1。因此，EB的降解受到特定酸碱催化的影响。在pH 4-11范围内，缓冲液浓度对EB的降解速率没有明显影响，但在pH 7以下观察到离子强度对其有一些影响。在pH 4或5及pH 10或11时，EB降解的表观活化能分别为14和19 kcal/mol。在pH 4-6范围内，EB通过两个乙烯亚胺环的顺序水解断裂降解为2, 5-二乙醇氨基-1, 4-苯醌。在pH 10-11范围内，EB通过两个乙烯亚胺环被羟基离子（自由基）顺序取代降解为2, 5-二羟基-1, 4-苯醌。在pH 7-9范围内，EB通过上述两种机制降解为2, 5-二乙醇氨基-1, 4-苯醌、2, 5-二羟基-1, 4-苯醌和2-乙醇氨基-5-羟基-1, 4-苯醌。
• Aziridinyl quinone antitumor agents based on indoles and cyclopent[b]indoles
  申请人：——

  公开号：US20030139609A1

  公开（公告）日：2003-07-24

  A large number of aziridinyl quinones represented by Series 1-9 were studied with respect to their DT-diaphorase substrate activity, DNA reductive alkylation, cytostatic/cytotoxic activity, and in vivo activity. As a result generalizations have been made with respect with respect to the following: DT-diaphorase substrate design, DT-diaphorase-cytotoxicity QSAR, and DNA reductive alkylating agent design. A saturating relationship exists between the substrate specificity for human recombinant DT-diaphorase and the cytotoxicity in the human H 460 non-small-cell lung cancer cell line. The interpretation of this relationship is that reductive activation is no longer rate limiting for substrates with high DT-diaphorase substrate specificities. High DT-diaphorase substrate specificity is not desirable in the indole and cylopent[b]indole systems because of the result is the loss of cancer selectivity along with increased toxicity. We conclude that aziridinyl quinones of this type should possess a substrate specificity (VMAX/KM )<10×10-4 s-1 for DT-diaphorase in order not to be too toxic or nonselective. While some DNA alkylation was required for cytostatic and cytotoxic activity by Series 1-9, too much alkylation results in loss of cancer selectivity as well as increased in vivo toxicity. Indeed, the most lethal compounds are the indole systems with a leaving group in the 3a-position (like the antitumor agent EO-9). We conclude that relatively poor DNA alkylating agents (according to our assay) show the lowest toxicity with the highest antitumor activity.

  研究了一系列1-9的大量环氧丙基喹喔啉类化合物，对它们的DT-二氢吡啶酰胺酶底物活性、DNA还原烷基化、细胞增殖/细胞毒性活性和体内活性进行了研究。结果得出了以下结论：DT-二氢吡啶酰胺酶底物设计、DT-二氢吡啶酰胺酶-细胞毒性QSAR和DNA还原烷基化剂设计。在人重组DT-二氢吡啶酰胺酶的底物特异性和人H460非小细胞肺癌细胞株的细胞毒性之间存在饱和关系。这种关系的解释是对于具有高DT-二氢吡啶酰胺酶底物特异性的底物，还原活化不再是速率限制步骤。对于吲哚和环戊[b]吲哚系统，高DT-二氢吡啶酰胺酶底物特异性并不理想，因为结果是癌症选择性的丧失以及毒性的增加。我们得出结论，这种类型的环氧丙基喹喔啉类化合物应该具有DT-二氢吡啶酰胺酶底物特异性（VMAX/KM）<10×10-4 s-1，以避免过于毒性或非选择性。虽然一些DNA烷基化是系列1-9的细胞增殖和细胞毒性活性所必需的，但过多的烷基化会导致癌症选择性的丧失以及体内毒性的增加。事实上，最致命的化合物是3a位有离去基团的吲哚系统（如抗肿瘤药物EO-9）。我们得出结论，相对较差的DNA烷基化剂（根据我们的测定）表现出最低的毒性和最高的抗肿瘤活性。