6-aminoquinazoline-5,8-dione | 1236813-56-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-aminoquinazoline-5,8-dione
• CAS: 1236813-56-1
• 化学式: C₈H₅N₃O₂
• 分子量: 175.147
• InChiKey: NDWWVJLQIUDUNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  85.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-aminoquinazoline-5,8-dione 、 丙酮 在 manganese triacetate 、 溶剂黄146 作用下， 反应 3.0h， 生成 7-methyl-5H-pyrrolo[2,3-g]quinazoline-5,9(6H)-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
• 作为产物：
  描述：

  喹唑啉-5,8-二酮 在 sodium azide 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以75%的产率得到6-aminoquinazoline-5,8-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of new cytotoxic azanaphthoquinone pyrrolo-annelated derivatives

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2010.05.003

文献信息

• Small molecule inducers of reactive oxygen species and inhibitors of mitochondrial activity
  申请人：The Regents of the University of Michigan

  公开号：US10781183B2

  公开（公告）日：2020-09-22

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.

  本发明属于药物化学领域。特别是，本发明涉及一类新的具有喹唑啉二酮结构的小分子，它们在癌细胞（如胰腺癌细胞）中可作为活性氧（ROS）诱导剂和线粒体活性抑制剂，并可用作治疗癌症（如胰腺癌）和其他疾病的疗法。
• SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY
  申请人：The Regents of the University of Michigan

  公开号：US20190308942A1

  公开（公告）日：2019-10-10

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.