5-(1-丁基苯并[cd]吲哚-2(1H)-亚基)-2,2-二甲基-1,3-二氧杂环己烷-4,6-二酮 | 1151666-45-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 5-(1-丁基苯并[cd]吲哚-2(1H)-亚基)-2,2-二甲基-1,3-二氧杂环己烷-4,6-二酮
• 中文别名: 5-(1-丁基苯并[CD]吲哚-2(1H)-亚基)-2,2-二甲基-1,3-二氧杂环己烷-4,6-二酮
• 英文名称: 1-butyl-2-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)-1H-benz[c,d]indole
• 英文别名: 5-(1-Butylbenzo[cd]indol-2(1H)-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione；5-(1-butylbenzo[cd]indol-2-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• CAS: 1151666-45-3
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: LALQDKCZCHTPEB-UHFFFAOYSA-N

物化性质

• 沸点：
  562.2±50.0 °C(Predicted)
• 密度：
  1.257

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1-丁基苯并[cd]吲哚-2(1H)-亚基)-2,2-二甲基-1,3-二氧杂环己烷-4,6-二酮 在 溶剂黄146 、 三氯氧磷 作用下， 反应 0.33h， 生成 (E)-2-(1-butylbenzo[c,d]indol-2(1H)-ylidene)acetaldehyde
  参考文献：
  名称：

  Second Generation G-Quadruplex Stabilizing Trimethine Cyanines

  摘要：

  G-四链 DNA 被认为是开发新型选择性化疗药物的一个非常吸引人的靶点，这可能显著减少对正常细胞的毒性。特别是，选择性结合 G-四链结构而不针对双链 DNA 的氰染料因其高度适应结构改造而受到关注，这使得对其生物分子相互作用进行微调成为可能。我们之前报道了设计用于通过末端堆叠相互作用有效结合 G-四链的五甲基和对称三甲基氰染料。在这里，我们报告了一种第二代药物候选物，即不对称三甲基氰染料。这些化合物已经合成并评估了它们的四链结合属性。引入苯[c,d]吲哚啉杂环单元提高了整体四链结合能力，而延长烷基链的长度则增加了四链与双链的结合特异性。

  DOI：

  10.1021/acs.bioconjchem.9b00571
• 作为产物：
  描述：

  2-(methylthio)benzindolium iodide 在 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 5-(1-丁基苯并[cd]吲哚-2(1H)-亚基)-2,2-二甲基-1,3-二氧杂环己烷-4,6-二酮
  参考文献：
  名称：

  Synthesis and evaluation of carbocyanine dyes as PRMT inhibitors and imaging agents

  摘要：

  Protein arginine methylation regulates multiple biological processes. Deregulation of protein arginine methyltransferase (PRMT) activities has been observed in many disease phenotypes. Small molecule probes that target PRMTs with strong affinity and selectivity can be used as valuable tools to dissect biological mechanisms of arginine methylation and establish the role of PRMT proteins in a disease process. In this work, we report synthesis and evaluation of a class of carbocyanine compounds containing indolium, benz[e]indolium or benz[c,d]indolium heterocyclic moieties that bind to the predominant arginine methyltransferase PRMT1 and inhibit its methyltransferase activity at low micromolar potencies. In particular, the developed molecules have long wavelength colorimetric and fluorometric photoactivities, which can be used for optical and near-infrared fluorescence imaging in cells or biological tissues. Together, these new chemical probes have potential application in PRMT studies both as enzyme inhibitors and as fluorescent dyes for microscope imaging. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.017

文献信息

• Functionalization of benzo[<i>c,d</i>]indole system for the synthesis of visible and near-infrared dyes
  作者：Maged Henary、Mariusz Mojzych、Martial Say、Lucjan Strekowski

  DOI：10.1002/jhet.39

  日期：2009.1

  A number of benzo[c,d]indolium derivatives have been synthesized. J. Heterocyclic Chem., 46, 84 (2009).

  已经合成了许多苯并[ c，d ]吲哚衍生物。杂环化学杂志，46，84（2009）。
• Second Generation G-Quadruplex Stabilizing Trimethine Cyanines
  作者：Eric A. Owens、Hang T. Huynh、Ekaterina M. Stroeva、Arghya Barman、Kostiantyn Ziabrev、Ananya Paul、Sarah V. Nguyen、Matthew Laramie、Donald Hamelberg、Markus W. Germann、W. David Wilson、Maged Henary

  DOI：10.1021/acs.bioconjchem.9b00571

  日期：2019.10.16

  G-Quadruplex DNA has been recognized as a highly appealing target for the development of new selective chemotherapeutics, which could result in markedly reduced toxicity toward normal cells. In particular, the cyanine dyes that bind selectively to G-quadruplex structures without targeting duplex DNA have attracted attention due to their high amenability to structural modifications that allows fine-tuning of their biomolecular interactions. We have previously reported pentamethine and symmetric trimethine cyanines designed to effectively bind G-quadruplexes through end stacking interactions. Herein, we are reporting a second generation of drug candidates, the asymmetric trimethine cyanines. These have been synthesized and evaluated for their quadruplex binding properties. Incorporating a benz[c,d]indolenine heterocyclic unit increased overall quadruplex binding, and elongating the alkyl length increases the quadruplex-to-duplex binding specificity.

  G-四链 DNA 被认为是开发新型选择性化疗药物的一个非常吸引人的靶点，这可能显著减少对正常细胞的毒性。特别是，选择性结合 G-四链结构而不针对双链 DNA 的氰染料因其高度适应结构改造而受到关注，这使得对其生物分子相互作用进行微调成为可能。我们之前报道了设计用于通过末端堆叠相互作用有效结合 G-四链的五甲基和对称三甲基氰染料。在这里，我们报告了一种第二代药物候选物，即不对称三甲基氰染料。这些化合物已经合成并评估了它们的四链结合属性。引入苯[c,d]吲哚啉杂环单元提高了整体四链结合能力，而延长烷基链的长度则增加了四链与双链的结合特异性。
• Synthesis and evaluation of carbocyanine dyes as PRMT inhibitors and imaging agents
  作者：Sarmistha Halder Sinha、Eric A. Owens、You Feng、Yutao Yang、Yan Xie、Yaping Tu、Maged Henary、Yujun George Zheng

  DOI：10.1016/j.ejmech.2012.06.017

  日期：2012.8

  Protein arginine methylation regulates multiple biological processes. Deregulation of protein arginine methyltransferase (PRMT) activities has been observed in many disease phenotypes. Small molecule probes that target PRMTs with strong affinity and selectivity can be used as valuable tools to dissect biological mechanisms of arginine methylation and establish the role of PRMT proteins in a disease process. In this work, we report synthesis and evaluation of a class of carbocyanine compounds containing indolium, benz[e]indolium or benz[c,d]indolium heterocyclic moieties that bind to the predominant arginine methyltransferase PRMT1 and inhibit its methyltransferase activity at low micromolar potencies. In particular, the developed molecules have long wavelength colorimetric and fluorometric photoactivities, which can be used for optical and near-infrared fluorescence imaging in cells or biological tissues. Together, these new chemical probes have potential application in PRMT studies both as enzyme inhibitors and as fluorescent dyes for microscope imaging. (C) 2012 Elsevier Masson SAS. All rights reserved.