1H-pyrrolo[3,2-g]isoquinoline-4,9-dione | 330455-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1H-pyrrolo[3,2-g]isoquinoline-4,9-dione
• CAS: 330455-16-8
• 化学式: C₁₁H₆N₂O₂
• 分子量: 198.181
• InChiKey: ROWIFTUWJPMSDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 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：
  62.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1H-pyrrolo[3,2-g]isoquinoline-4,9-dione 在 四丁基氟化铵 、 sodium hydride 、 三乙胺 作用下， 生成 7-(4,9-Dioxopyrrolo[3,2-g]isoquinolin-1-yl)heptyl methanesulfonate
  参考文献：
  名称：

  Synthesis and antiproliferative activity of new cytotoxic azanaphthoquinone pyrrolo-annelated derivatives: Part II

  摘要：

  A series of 6-azanaphthoquinone pyrrolo-annelated derivatives carrying different basic side chains have been synthesized. The antiproliferative activities of all compounds were evaluated on at least four different cell lines with Mitoxantrone as reference compound. Cytotoxic effects and DNA intercalation behavior were investigated. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.013
• 作为产物：
  描述：

  5,8-二氢异喹啉-5,8-二酮 在 sodium azide 、 manganese triacetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 生成 1H-pyrrolo[3,2-g]isoquinoline-4,9-dione
  参考文献：
  名称：

  Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains

  摘要：

  Recent clinical approvals of brain imaging radiotracers targeting amyloid-beta provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-beta aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-beta aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-beta plaques in brain sections of APP/PS1 double transgenic Alzheimer's mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-beta imaging agents for early stage Alzheimer's.

  DOI：

  10.1021/acschemneuro.9b00093

文献信息

• Synthesis of Azanaphthoquinone Annelated Pyrroles
  作者：Helmut Spreitzer、Andrea Pichler、Wolfgang Holzer、Martin Kratzel、Rita Slanz、Alexandra Koulouri、Petra Krenn、Ulrike Parrer、Petra Szieber

  DOI：10.3987/com-98-8401

  日期：——

  The synthesis of azanaphthoquinone annelated pyrrole derivatives is described. The [c]-annelated derivative was synthesized by reaction of an azanaphthoquinone monoketal with tosylmethyl isocyanide. The synthesis of each of the two isomeric [b]-annelated pyrrole derivatives was realized by selective acylation reactions with pyrrole. Furthermore detailed NMR spectroscopic studies (H-1,C-13) are published.
• Synthesis and biological evaluation of novel cytotoxic azanaphthoquinone annelated pyrrolo oximes
  作者：Karem Shanab、Nipawan Pongprom、Eva Wulz、Wolfgang Holzer、Helmut Spreitzer、Peter Schmidt、Babette Aicher、Gilbert Müller、Eckhard Günther

  DOI：10.1016/j.bmcl.2007.09.054

  日期：2007.11

  Two series of azanaphthoquinone annelated pyrrolo oximes have been synthesized. The antiproliferative activities of 10 compounds were evaluated on at least four different cell lines. One series of pyrrolo derivatives showed high cytotoxic activity. The effects on cell cycle and caspase activity were investigated. Compounds 9a and 9b showed an accumulation of cells in G2/M phase. Substantial and dose-dependent caspase activity was found after treatment of cells with 9a and 9b. This indicates an apoptosis inducing property of these compounds. (C) 2007 Published by Elsevier Ltd.
• Synthesis and biological evaluation of new cytotoxic azanaphthoquinone pyrrolo-annelated derivatives
  作者：Karem Shanab、Eva Schirmer、Heike Knafl、Eva Wulz、Wolfgang Holzer、Helmut Spreitzer、Peter Schmidt、Babette Aicher、Gilbert Müller、Eckhard Günther

  DOI：10.1016/j.bmcl.2010.05.003

  日期：2010.7

  A series of azanaphthoquinone pyrrolo-annelated derivatives attached to basic side chains have been synthesized. The antiproliferative activities of all compounds were evaluated on at least four different cell lines. The effects on cell cycle and intercalation were investigated. (c) 2010 Elsevier Ltd. All rights reserved.
• Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains
  作者：Naewoo Neo Shin、Hanna Jeon、Youngeun Jung、Seungyeop Baek、Sejin Lee、Hee Chan Yoo、Gi Hun Bae、Keunwan Park、Seung-Hoon Yang、Jung Min Han、Ikyon Kim、YoungSoo Kim

  DOI：10.1021/acschemneuro.9b00093

  日期：2019.6.19

  Recent clinical approvals of brain imaging radiotracers targeting amyloid-beta provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-beta aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-beta aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-beta plaques in brain sections of APP/PS1 double transgenic Alzheimer's mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-beta imaging agents for early stage Alzheimer's.
• Synthesis and antiproliferative activity of new cytotoxic azanaphthoquinone pyrrolo-annelated derivatives: Part II
  作者：Karem Shanab、Eva Schirmer、Eva Wulz、Barbara Weissenbacher、Sigrid Lassnig、Rita Slanz、Germana Fösleitner、Wolfgang Holzer、Helmut Spreitzer、Peter Schmidt、Babette Aicher、Gilbert Müller、Eckhard Günther

  DOI：10.1016/j.bmcl.2011.03.013

  日期：2011.5

  A series of 6-azanaphthoquinone pyrrolo-annelated derivatives carrying different basic side chains have been synthesized. The antiproliferative activities of all compounds were evaluated on at least four different cell lines with Mitoxantrone as reference compound. Cytotoxic effects and DNA intercalation behavior were investigated. (C) 2011 Elsevier Ltd. All rights reserved.

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