7-acetamido-4-(2-furanyl)-8-hydroxyquinoline

• 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: 7-acetamido-4-(2-furanyl)-8-hydroxyquinoline
• 英文别名: N-[4-(furan-2-yl)-8-hydroxyquinolin-7-yl]acetamide
• 化学式: C₁₅H₁₂N₂O₃
• 分子量: 268.272
• InChiKey: NULUGSPBHVGIMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-硝基水杨酸 在 lithium hydroxide monohydrate 、 叠氮磷酸二苯酯 、 palladium diacetate 、 三溴化硼 、 三溴化磷 、 铁粉 、 potassium carbonate 、 氯化铵 、 caesium carbonate 、 溶剂黄146 、 三氟乙酸 、 1,2-双(二苯基膦)乙烷 、 三甲胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二苯醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 叔丁醇 为溶剂， 反应 50.75h， 生成 7-acetamido-4-(2-furanyl)-8-hydroxyquinoline
  参考文献：
  名称：

  Drug Design Targeting T-Cell Factor-Driven Epithelial–Mesenchymal Transition as a Therapeutic Strategy for Colorectal Cancer

  摘要：

  Metastasis is the cause of 90% of mortality in cancer patients. For metastatic colorectal cancer (mCRC), the standard-of-care drug therapies only palliate the symptoms but are ineffective, evidenced by a low survival rate of similar to 11%. T-cell factor (TCF) transcription is a major driving force in CRC, and we have characterized it to be a master regulator of epithelial-mesenchymal transition (EMT). EMT transforms relatively benign epithelial tumor cells into quasi-mesenchymal or mesenchymal cells that possess cancer stem cell properties, promoting multidrug resistance and metastasis. We have identified topoisomerase II alpha (TOP2A) as a DNA-binding factor required for TCF-transcription. Herein, we describe the design, synthesis, biological evaluation, and in vitro and in vivo pharmacokinetic analysis of TOP2A ATP-competitive inhibitors that prevent TCF-transcription and modulate or reverse EMT in mCRC. Unlike TOP2A poisons, ATP-competitive inhibitors do not damage DNA, potentially limiting adverse effects. This work demonstrates a new therapeutic strategy targeting TOP2A for the treatment of mCRC and potentially other types of cancers.

  DOI：

  10.1021/acs.jmedchem.9b01065

文献信息

• [EN] TOPOISOMERASE II-alpha INHIBITORS AND METHODS OF TREATING CANCER USING THE SAME<br/>[FR] INHIBITEURS DE LA TOPOISOMÉRASE II-ALPHA ET MÉTHODES DE TRAITEMENT DU CANCER À L'AIDE DE CES INHIBITEURS
  申请人：UNIV COLORADO REGENTS

  公开号：WO2020205991A1

  公开（公告）日：2020-10-08

  A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof, having the chemical structure of formula I as defined in the text and methods of using these compounds to inhibit topoisomerase IIα and treat or prevent metastasis of cancer in a subject.

  一种具有化学结构为式I所定义的化合物，或其药用可接受的盐、溶剂合物或前药，以及使用这些化合物来抑制拓扑异构酶IIα并治疗或预防受试者的癌症转移的方法。
• Drug Design Targeting T-Cell Factor-Driven Epithelial–Mesenchymal Transition as a Therapeutic Strategy for Colorectal Cancer
  作者：Adedoyin D. Abraham、Hector Esquer、Qiong Zhou、Nicholas Tomlinson、Brayden D. Hamill、Joshua M. Abbott、Linfeng Li、Laura A. Pike、Sébastien Rinaldetti、Dominique A. Ramirez、Paul J. Lunghofer、Jose D. Gomez、Jerome Schaack、Travis Nemkov、Angelo D’Alessandro、Kirk C. Hansen、Daniel L. Gustafson、Wells A. Messersmith、Daniel V. LaBarbera

  DOI：10.1021/acs.jmedchem.9b01065

  日期：2019.11.27

  Metastasis is the cause of 90% of mortality in cancer patients. For metastatic colorectal cancer (mCRC), the standard-of-care drug therapies only palliate the symptoms but are ineffective, evidenced by a low survival rate of similar to 11%. T-cell factor (TCF) transcription is a major driving force in CRC, and we have characterized it to be a master regulator of epithelial-mesenchymal transition (EMT). EMT transforms relatively benign epithelial tumor cells into quasi-mesenchymal or mesenchymal cells that possess cancer stem cell properties, promoting multidrug resistance and metastasis. We have identified topoisomerase II alpha (TOP2A) as a DNA-binding factor required for TCF-transcription. Herein, we describe the design, synthesis, biological evaluation, and in vitro and in vivo pharmacokinetic analysis of TOP2A ATP-competitive inhibitors that prevent TCF-transcription and modulate or reverse EMT in mCRC. Unlike TOP2A poisons, ATP-competitive inhibitors do not damage DNA, potentially limiting adverse effects. This work demonstrates a new therapeutic strategy targeting TOP2A for the treatment of mCRC and potentially other types of cancers.