2-bromo-anthracene-1,4-dione | 55696-06-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 2-bromo-anthracene-1,4-dione
• 英文别名: 2-bromoanthracene-1,4-dione；2-bromo-1,4-anthraquinone；2-Brom-1,4-anthrachinon；2-Brom-anthrachinon-(1,4)
• CAS: 55696-06-5
• 化学式: C₁₄H₇BrO₂
• 分子量: 287.112
• InChiKey: SXIYBQQMSNJRBF-UHFFFAOYSA-N

物化性质

• 沸点：
  426.7±45.0 °C(Predicted)
• 密度：
  1.698±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-anthracene-1,4-dione 在 sodium hydroxide 、 溴 、 potassium carbonate 作用下， 以 溶剂黄146 、 二甲基亚砜 为溶剂， 生成 2-(3,5-Ditert-butyl-4-hydroxyphenyl)-3-methoxyanthracene-1,4-dione
  参考文献：
  名称：

  Wurm; Probst; Schwandt, Pharmazie, 2001, vol. 56, # 7, p. 527 - 533

  摘要：

  DOI：
• 作为产物：
  描述：

  1,4-蒽醌 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 2.5h， 以81%的产率得到2-bromo-anthracene-1,4-dione
  参考文献：
  名称：

  合成具有抗锥虫和抗利什曼活性的2-苯氧基-1,4-萘醌和2-苯氧基-1,4-蒽醌小文库。

  摘要：

  利用显示抗锥虫活性的天然产物的结构特征，我们设计并合成了一个小的2-苯氧基-1,4-萘醌和2-苯氧基-1,4-蒽醌衍生物文库。该文库是通过并行方法并使用容易获得的合成子获得的。所有衍生物均对锥虫或利什曼原虫种均显示抑制活性，其中8、10和16是对布鲁氏锥虫，杜氏利什曼原虫和克鲁氏锥虫细胞最具活性的化合物（IC（50）= 50nM，IC（50）=分别为0.28 microM和IC（50）= 1.26 microM）。

  DOI：

  10.1016/j.bmcl.2008.03.009

文献信息

• Toward the Development of Dual-Targeted Glyceraldehyde-3-phosphate Dehydrogenase/Trypanothione Reductase Inhibitors against<i>Trypanosoma brucei</i>and<i>Trypanosoma cruzi</i>
  作者：Federica Belluti、Elisa Uliassi、Giacomo Veronesi、Christian Bergamini、Marcel Kaiser、Reto Brun、Angelo Viola、Romana Fato、Paul A. M. Michels、R. Luise Krauth-Siegel、Andrea Cavalli、Maria Laura Bolognesi

  DOI：10.1002/cmdc.201300399

  日期：2014.2

  dehydrogenase/trypanothione reductase (GAPDH/TR). These enzymes belong to metabolic pathways that are vital to Trypanosoma brucei and Trypanosoma cruzi, and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual‐target antitrypanosomal profile, both in enzyme assays and in in vitro parasite cultures. The merged derivative 2‐[3‐(3‐dimethylaminopropoxy)‐2‐oxo‐2H

  硝呋替莫–氟鸟氨酸联合疗法（NECT）的最新开发已实现了锥虫病治疗的显着改善。作为药物组合的替代方法和克服大多数抗锥虫病药物发现挑战的方法，已经设想了多目标药物设计策略。为了开始验证该假设，我们设计并开发了一系列针对3-磷酸甘油醛脱氢酶/锥虫硫酮还原酶（GAPDH / TR）的醌-香豆素杂种。这些酶属于对布鲁氏锥虫和克氏锥虫至关重要的代谢途径，因此被认为是有前途的药物靶标。合成的分子在酶测定和体外寄生虫培养中均具有双重靶点抗锥虫体特征。合并后的衍生物：2 - [3-（3-二甲氨基丙氧基）-2-氧代-2- ħ -苯并吡喃-7-基]氧基}蒽-1,4-二酮（10）表现出的IC 50为5.4值μ中号对铽GAPDH和伴随ķ我的2.32值μ中号对锝TR。值得注意的是，2- 4- [6- [2-（2-二甲基氨基乙氧基）-2-oxo-2 H-铬n-3-基]苯氧基}蒽-1,4-二酮（化合物6）表现出了卓越的EC
• Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase ( Tb GAPDH) and Trypanosoma cruzi trypanothione reductase ( Tc TR) and display trypanocidal activity
  作者：Elisa Uliassi、Giulia Fiorani、R. Luise Krauth-Siegel、Christian Bergamini、Romana Fato、Giulia Bianchini、J. Carlos Menéndez、Maria Teresa Molina、Eulogio López-Montero、Federico Falchi、Andrea Cavalli、Sheraz Gul、Maria Kuzikov、Bernhard Ellinger、Gesa Witt、Carolina B. Moraes、Lucio H. Freitas-Junior、Chiara Borsari、Maria Paola Costi、Maria Laura Bolognesi

  DOI：10.1016/j.ejmech.2017.10.005

  日期：2017.12

  that its pentacyclic core possesses structural resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual-targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR). Following this basic idea, we synthesized a small library of crassiflorone derivatives 15-23 and investigated their

  Crassiflorone是一种具有抗分枝杆菌和抗性腺功能的天然产品，从非洲黑檀Diospyros crassiflora的茎皮中分离出来。我们注意到它的五环核与醌-香豆素杂种3具有相似的结构，我们报道该杂种对布鲁氏锥虫甘油醛-3-磷酸脱氢酶（Tb GAPDH）和克氏锥虫锥虫对硫磷还原酶（Tc TR）表现出双重靶向抑制作用。。根据这一基本思想，我们合成crassiflorone衍生物的小型图书馆15 - 23，并研究其潜在的抗锥虫药。19是该系列中唯一的化合物，在10μM时显示出平衡的双重分布（％抑制Tb GAPDH  = 64％和％Tc TR  = 65％）。 在表型分析中，活性最高的化合物是18和21，在5μM时，它们分别抑制Tb血流形式的生长29％和38％。值得注意的是，所有新合成的10μM化合物均未分别影响人A549和786-O细胞系的生存力和线粒体状态。但是，需要进一步优化以解决
• Conjugation of Quinones with Natural Polyamines: Toward an Expanded Antitrypanosomatid Profile
  作者：Federica Lizzi、Giacomo Veronesi、Federica Belluti、Christian Bergamini、Almudena López-Sánchez、Marcel Kaiser、Reto Brun、R. Luise Krauth-Siegel、Dennis G. Hall、Luis Rivas、Maria Laura Bolognesi

  DOI：10.1021/jm301112z

  日期：2012.12.13

  A combinatorial library of quinone-polyamine conjugates designed to optimize the antitrypanosomatid profile of hit compounds 1 and 2 has been prepared by a solid-phase approach. The conjugates were evaluated against the three most important human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani), and several showed promising activity. A subset also inhibited trypanothione reductase in vitro and induced oxidase activity of the enzyme. A highly potent analogue (7) was identified with activity against T. brucei as low as 70 nM and a selectivity index of 72. Interestingly, the presence of a cadaverine tail confers to 7 the ability to target mitochondrial function in Leishmania. In fact, in L. donovani promastigotes, we verified for 7 a decrease of cytoplasmic ATP and mitochondrial potential. Therefore, the current results support the suitability of the conjugation approach for the development of novel polyamine conjugates with enhanced therapeutic potential.
• 2-Phenoxy-1,4-naphthoquinones: From a Multitarget Antitrypanosomal to a Potential Antitumor Profile
  作者：Federica Prati、Christian Bergamini、Maria Teresa Molina、Federico Falchi、Andrea Cavalli、Marcel Kaiser、Reto Brun、Romana Fato、Maria Laura Bolognesi

  DOI：10.1021/acs.jmedchem.5b00748

  日期：2015.8.27

  A small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile of the multitarget hit compound B6 (1). The whole series was evaluated against the three most important human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani), and two compounds (14 and 21) showed good activity, despite a concomitant mammalian cytotoxicity. Furthermore, a subset also inhibited the glycolytic TbGAPDH enzyme in vitro. In light of these results and aware of the antitumor properties of quinones, the anticancer potential of some selected derivatives was investigated. Intriguingly, the tested compounds displayed antitumor activity, while being less toxic against noncancerous cells. The observed cytotoxic potency was ascribed to a multitarget mechanism of action accounting for hGAPDH inhibition and mitochondrial toxicity. Overall, the development of further derivatives, able to finely modulate multiple pathways of cancer or parasite cell metabolism, might lead to more effective treatments against these devastating diseases.
• [EN] COMPUESTOS QUINÓNICOS ANTITUMORALES Y SUS DERIVADOS, PROCEDIMIENTO DE OBTENCIÓN Y SUS APLICACIONES<br/>[ES] COMPUESTOS QUINONICOS ANTITUMORALES Y SUS D invenciÌn ERIVADOS, PROCEDIMIENTO DE OBTENCION Y SUS APLICACIONES<br/>[FR] COMPOSES QUINONIQUES ANTITUMORAUX ET LEURS DERIVES, PROCEDE D'OBTENTION DE CEUX-CI ET APPLICATIONS CORRESPONDANTES
  申请人：CONSEJO SUPERIOR INVESTIGACION

  公开号：WO2007026041A2

  公开（公告）日：2007-03-08

  [EN] The invention relates to derivative 1,4-dioxaanthracene compounds, mainly 1,4-anthraquinoids, having formula I as tumour cell growth inhibitors. The invention also relates to methods of preparing said compounds, pharmaceutical compositions containing same and the clinical uses thereof as antitumour and antiparasitic agents.
  [FR] L'invention concerne des composés dérivés de 1,4-dioxyanthracéniques, principalement de 1,4-anthraquinoniques, de formule (I) en tant qu'inhibiteurs de croissance de cellules tumorales, ainsi que des procédés utiles à leur préparation, des compositions pharmaceutiques les contenant et leurs applications cliniques en tant qu'antitumoraux et antiparasitaires.
  [ES] La presente invención describe unos compuestos derivados 1,4- dioxaantracénicós, principalmente 1, 4-antraquinónicos, de formula I como inhibidores del crecimiento de células tumorales, asi como a procedimientos utiles para su preparación, composiciones farmaceuticas que los contienen y sus aplicaciones clinicas como antitumoral y antiparasitario.