化合物P62-MEDIATEDMITOPHAGYINDUCER | 1809031-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 化合物P62-MEDIATEDMITOPHAGYINDUCER
• 中文别名: 化合物P62-MEDIATEDMITOPHAGYINDUCER
• 英文名称: 1-(3-iodophenyl)-4-(3-nitrophenyl)-1,2,3-triazole
• 英文别名: 1-(3-iodophenyl)-4-(3-nitrophenyl)-1H-1,2,3-triazole；P62-mediated mitophagy inducer；1-(3-iodophenyl)-4-(3-nitrophenyl)triazole
• CAS: 1809031-84-2
• 化学式: C₁₄H₉IN₄O₂
• 分子量: 392.156
• InChiKey: LSVWEYNSNZJEGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-碘-3-硝基苯 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 copper(ll) sulfate pentahydrate 、 potassium carbonate 、 三乙胺 、 维生素 C 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 23.5h， 生成 化合物P62-MEDIATEDMITOPHAGYINDUCER
  参考文献：
  名称：

  A Comparative Assessment Study of Known Small-Molecule Keap1−Nrf2 Protein–Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

  摘要：

  Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance-and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

  DOI：

  10.1021/acs.jmedchem.9b00723

文献信息

• Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1–Nrf2 Protein–Protein Interaction
  作者：Hélène C. Bertrand、Marjolein Schaap、Liam Baird、Nikolaos D. Georgakopoulos、Adrian Fowkes、Clarisse Thiollier、Hiroko Kachi、Albena T. Dinkova-Kostova、Geoff Wells

  DOI：10.1021/acs.jmedchem.5b00602

  日期：2015.9.24

  The transcription factor Nrf2 regulates the expression of a large network of cytoprotective and metabolic enzymes and proteins. Compounds that directly and reversibly inhibit the interaction between Nrf2 and its main negative regulator Keap1 are potential pharmacological agents for a range of disease types including neurodegenerative conditions and cancer. We describe the development of a series of 1,4-dipheny1-1,2,3-triazole compounds that inhibit the Nrf2-Keap1 protein protein interaction (PPI) in vitro and in live cells and up-regulate the expression of Nrf2-dependent gene products.