N,N'-(naphthalene-1,4-diyl)dibenzenesulfonamide | 167321-72-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N,N'-(naphthalene-1,4-diyl)dibenzenesulfonamide
• 英文别名: N-[4-(benzenesulfonamido)naphthalen-1-yl]benzenesulfonamide
• CAS: 167321-72-4
• 化学式: C₂₂H₁₈N₂O₄S₂
• 分子量: 438.528
• InChiKey: OZHNDJFQAQOYJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-(naphthalene-1,4-diyl)dibenzenesulfonamide 在 chloramine-B 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以91%的产率得到N,N'-bis(phenylsulfonyl)-1,4-naphthoquinone diimine
  参考文献：
  名称：

  Kremlev, M. M.; Moskalenko, A. I.; Bezverkhii, N. P., Journal of Organic Chemistry USSR (English Translation), 1980, vol. 16, p. 1639 - 1640

  摘要：

  DOI：
• 作为产物：
  描述：

  1-氨基-4-硝基萘 在 吡啶 、 palladium on activated charcoal 、 氢气 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 N,N'-(naphthalene-1,4-diyl)dibenzenesulfonamide
  参考文献：
  名称：

  磷酸化 p62 和 Keap1 之间蛋白质-蛋白质相互作用的抑制剂减弱人肝细胞癌细胞系的化学抗性

  摘要：

  摘要 对抗癌药物的耐药性一直是开发治疗方法和降低医疗成本的障碍。虽然索拉非尼用于治疗人类肝细胞癌 (HCC)，但耐药性限制了其疗效。p62 是一种多功能蛋白，在几种 HCC 细胞系（例如 Huh-1 细胞）中过表达。磷酸化的 p62 ( p -p62) 抑制 Keap1 和 Nrf2 之间的蛋白质-蛋白质相互作用 (PPI)，导致 Nrf2 过度激活，从而导致耐药性。我们发现了一种独特的 Nrf2 灭活剂，名为 K67，它抑制了 Keap1 和p之间的 PPI-p62 并减弱 Huh-1 细胞中的索拉非尼耐药性。在此，我们通过修饰 K67 的两个苯磺酰基的 4 位取代基，设计并合成了新型 K67 衍生物。尽管这些新衍生物抑制 Keap1- p- p62 PPI 的水平与 K67 相当或更弱，但异丙氧基衍生物比 K67 更大程度地增强了 Huh-1 细胞对索拉非尼的敏感性，而对细胞活力没有任何影响。

  DOI：

  10.1080/10715762.2020.1732955

文献信息

• Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators
  作者：Atul D. Jain、Haranatha Potteti、Benjamin G. Richardson、Laura Kingsley、Julia P. Luciano、Aya F. Ryuzoji、Hyun Lee、Aleksej Krunic、Andrew D. Mesecar、Sekhar P. Reddy、Terry W. Moore

  DOI：10.1016/j.ejmech.2015.08.049

  日期：2015.10

  Activation of the transcription factor Nrf2 has been posited to be a promising therapeutic strategy in a number of inflammatory and oxidative stress diseases due to its regulation of detoxifying enzymes. In this work, we have developed a comprehensive structure activity relationship around a known, naphthalene-based non-electrophilic activator of Nrf2, and we report highly potent non-electrophilic activators of Nrf2. Computational docking analysis of a subset of the compound series demonstrates the importance of water molecule displacement for affinity, and the X-ray structure of di-amide 12e supports the computational analysis. One of the best compounds, acid 16b, has an IC50 of 61 nM in a fluorescence anisotropy assay and a K-d of 120 nM in a surface plasmon resonance assay. Additionally, we demonstrate that the ethyl ester of 16b is an efficacious inducer of Nrf2 target genes, exhibiting ex vivo efficacy similar to the well-known electrophilic activator, sulforaphane. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Structure–Activity and Structure–Property Relationship and Exploratory in Vivo Evaluation of the Nanomolar Keap1–Nrf2 Protein–Protein Interaction Inhibitor
  作者：Zheng-Yu Jiang、Li−Li Xu、Meng-Chen Lu、Zhi-Yun Chen、Zhen-Wei Yuan、Xiao-Li Xu、Xiao-Ke Guo、Xiao-Jin Zhang、Hao-Peng Sun、Qi-Dong You

  DOI：10.1021/acs.jmedchem.5b00185

  日期：2015.8.27

  Directly disrupting the Keap1-Nrf2 protein protein interaction (PPI) is an effective way to activate Nrf2. Using the potent Keap1-Nrf2 PPI inhibitor that was reported by our group, we conducted a preliminary investigation of the structure activity and structure property relationships of the ring systems to improve the drug-like properties. Compound 18e, which bore p-acetamido substituents on the side chain phenyl rings, was the best choice for balancing PPI inhibition activity, physicochemical properties, and cellular Nrf2 activity. Cell-based experiments with 18e showed that the Keap1-Nrf2 PPI inhibitor can activate Nrf2 and induce the expression of Nrf2 downstream proteins in an Nrf2-dependent manner. An exploratory in vivo experiment was carried out to further evaluate the anti-inflammatory effects of 18e in a LPS-challenged mouse model. The primary results indicated that 18e could reduce the level of circulating pro-inflammatory cytokines induced by LPS and relieve the inflammatory response.
• Experiments with Derivatives of Quinone Imides
  作者：Ahmed Mustafa、Mohamed Kamel

  DOI：10.1021/ja01108a045

  日期：1953.6
• Avdeenko, A. P.; Velichko, N. V., Russian Journal of Organic Chemistry, 1994, vol. 30, # 7.2, p. 1100 - 1104
  作者：Avdeenko, A. P.、Velichko, N. V.

  DOI：——

  日期：——
• Quinone Imides. III. 1,4-Naphthoquinone Disulfonimides
  作者：Roger Adams、R. A. Wankel

  DOI：10.1021/ja01145a048

  日期：1951.1