1,4-dimethylquinoline-2,5,8(1H)-trione | 157463-91-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,4-dimethylquinoline-2,5,8(1H)-trione
• 英文别名: 1,4-dimethyl-2,5,8(1H)quinolinetrione；Quinone, 12；1,4-dimethylquinoline-2,5,8-trione
• CAS: 157463-91-7
• 化学式: C₁₁H₉NO₃
• 分子量: 203.197
• InChiKey: PWQQNOLPFIDYHD-UHFFFAOYSA-N

物化性质

• 沸点：
  393.2±41.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-dimethylquinoline-2,5,8(1H)-trione 在 双氧水 、 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

  摘要：

  In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b] furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control beta-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H... pi interactions with Trp105 and Phe178 residues compared to the control beta-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.004
• 作为产物：
  描述：

  N-(2,5-二甲氧基苯基)甲酰胺 在 potassium dichromate 、 lithium aluminium tetrahydride 、 硫酸 、 氢溴酸 作用下， 以 乙醚 、 水 、 xylene 为溶剂， 反应 54.17h， 生成 1,4-dimethylquinoline-2,5,8(1H)-trione
  参考文献：
  名称：

  Regioselectivity of the Diels-Alder reactions of 2,5,8(1H)-quinolinetriones

  摘要：

  Diels-Alder reactions of 2,5,8(1H)-quinolinetriones were completely regioselective for all the unsymmetrical dienes tested, except in the case of isoprene. This corresponds to a level of regioselectivity higher than the one found by previous workers for 5,8-quinolinequinone.

  DOI：

  10.1016/s0040-4020(01)85276-5

文献信息

• Regioselective Diels–Alder reactions of 3-indolylquinones
  作者：Miguel Ángel Alonso、Pilar López-Alvarado、Carmen Avendaño、J.Carlos Menéndez

  DOI：10.1016/s0040-4020(03)00340-5

  日期：2003.4

  6-(3-Indolyl)quinolinequinone derivatives gave regioselective Diels–Alder reactions with a variety of dienophiles, yielding polycyclic carbazole derivatives. One-pot reactions, proceeding through a cascade of reactions including regioselective Michael and Diels–Alder steps, gave heptacyclic derivatives starting from indoles and 2,5,8(1H)-quinolinetriones. Double Diels–Alder reactions of 6-(3-indolyl)quinolinequinones

  6-（3-吲哚基）喹啉醌衍生物可与多种亲二烯体进行区域选择性Diels-Alder反应，生成多环咔唑衍生物。一锅式反应通过一系列反应（包括区域选择性Michael和Diels-Alder步骤）进行，从吲哚和2,5,8（1 H）-喹啉三酮类化合物开始生成七环衍生物。Double Diels-6-（3-吲哚基）喹啉醌和二卤代苯醌的阿尔德反应一步生成11个环的产物。
• One-pot assembly of large heterocyclic quinones through three-component reactions
  作者：Pilar López-Alvarado、Miguel Ángel Alonso、Carmen Avendaño、J.Carlos Menéndez

  DOI：10.1016/s0040-4039(01)01725-7

  日期：2001.11

  5,8-quinolinetriones in the presence of a catalytic amount of hydrochloric acid afforded heptacyclic reaction products arising from a cascade of two regioselective Michael addition–Diels–Alder cycloaddition steps. In another approach to polyheterocyclic quinone systems, double Diels–Alder reactions between indolylquinolinetriones and 2,5- or 2,6-dihalogenated benzoquinones provided regioisomeric 11-cycle

  在催化量的盐酸存在下，用2,5,8-喹啉三酮处理吲哚可得到由两个区域选择性迈克尔加成–狄尔斯–阿尔德环加成步骤组成的级联反应的七环反应产物。在另一种用于多杂环醌系统的方法中，吲哚基喹啉三酮与2,5-或2,6-二卤代苯醌之间的双重Diels-Alder反应可提供高产率的区域异构11环产物。
• Structure-Antitumor Activity Relationships of Aza- and Diaza-Anthracene-2,9,10-Triones and Their Partially Saturated Derivatives
  作者：Carmen Avendaño、Pilar López-Alvarado、José María Pérez、Miguel Ángel Alonso、Eva Pascual-Alfonso、Miriam Ruiz-Serrano、J. Carlos Menéndez

  DOI：10.3390/molecules29020489

  日期：——

  relationships. From the results obtained, we conclude that some representatives of the 1,8-diazaanthracene-2,9,10-trione framework show potent and selective cytotoxicity against solid tumors. Similar findings were made for the related 1-azaanthracene-2,9,10-trione derivatives, structurally similar to the marcanine natural products, which showed improved activity over their natural counterparts. An enantioselective

  1,8-二氮杂蒽-2,9,10-三酮，它们的 5,8-二氢衍生物和 1,8-二氮杂蒽-2,7,9,10-四酮，在结构上与二氮杂喹啉菌素家族天然产物相关，采用 Diels-Alder 策略以区域选择性方式合成。研究了这些文库在各种人类癌细胞系中的细胞毒性，以建立结构-活性关系。从获得的结果中，我们得出结论，1,8-二氮杂蒽-2,9,10-三酮框架的一些代表对实体瘤显示出有效的选择性细胞毒性。相关的 1-氮杂蒽-2,9,10-三酮衍生物也发现了类似的结果，它们在结构上与 marcanine 天然产物相似，其活性优于天然产物。针对手性 5 取代的 1,8-二杂蒽-2,9,10-三酮的情况开发了一种基于使用 SAMP 相关手性衍生的对映选择性方案，并表明它们的细胞毒性不是对映特异性的。
• Synthesis of Casimiroin and Optimization of Its Quinone Reductase 2 and Aromatase Inhibitory Activities
  作者：Arup Maiti、P. V. Narasimha Reddy、Megan Sturdy、Laura Marler、Scott D. Pegan、Andrew D. Mesecar、John M. Pezzuto、Mark Cushman

  DOI：10.1021/jm801335z

  日期：2009.4.9

  An efficient method has been developed to synthesize casimiroin (1), a component of the edible fruit of Casimiroa edulis, on a multigram scale in good overall yield. The route was versatile enough to provide an array of compound 1 analogues that were evaluated as QR2 and aromatase inhibitors. In addition, X-ray crystallography studies of QR2 in complex with compound 1 and one of its more potent analogues has provided insight into the mechanism of action of this new series of QR2 inhibitors. The initial biological investigations suggest that compound 1 and its analogues merit further investigation as potential chemopreventive or chemotherapeutic agents.
• Perez Jose Maria, Vidal Luis, Grande Mercedes T., Menendez J. Carlos, Ave+, Tetrahedron, 50 (1994) N 26, S 7923-7932
  作者：Perez Jose Maria, Vidal Luis, Grande Mercedes T., Menendez J. Carlos, Ave+

  DOI：——

  日期：——