N,N'-(naphthalene-1,4-diyl)bis(4-chlorobenzenesulfonamide) | 167321-71-3

• 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)bis(4-chlorobenzenesulfonamide)
• 英文别名: 4-chloro-N-(4-(((4-chlorophenyl)sulfonyl)amino)1-naphthyl)benzenesulfonamide；4-chloro-N-[4-[(4-chlorophenyl)sulfonylamino]naphthalen-1-yl]benzenesulfonamide
• CAS: 167321-71-3
• 化学式: C₂₂H₁₆Cl₂N₂O₄S₂
• 分子量: 507.418
• InChiKey: XNUCDMDHVWJDIP-UHFFFAOYSA-N

物化性质

• 沸点：
  686.0±65.0 °C(Predicted)
• 密度：
  1.557±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 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)bis(4-chlorobenzenesulfonamide) 以76%的产率得到
  参考文献：
  名称：

  Awdeenko A. P., Welitschko N. W., Zh. organ. khimii, 30 (1994) N 7, S 1042-1045

  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)bis(4-chlorobenzenesulfonamide)
  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

• Carboxylesterase inhibitors
  申请人：Potter M. Philip

  公开号：US20050054691A1

  公开（公告）日：2005-03-10

  This disclosure relates to amides, aryl sulphonamides, aryl ureas, and α,β-diketones derivatives useful as carboxylesterase esterase inhibitors. The disclosure is also directed to the use of these compounds as selective human intestinal carboxylesterase inhibitors and insect carboxylesterase inhibitors. The disclosure is also directed to pharmaceutical compositions and pesticide formulations containing these compounds, and to methods for treating or ameliorating the toxic effects following administration of drugs such as cancer therapy drugs, treating or ameliorating the effects of a drug overdose, and to the use of the compounds for increasing the effectiveness of insecticides and pesticides.

  本公开涉及可用作羧酸酯酶抑制剂的酰胺类、芳基磺酰胺类、芳基脲类和 α,β-二酮衍生物。本发明还涉及这些化合物作为选择性人体肠道羧酯酶抑制剂和昆虫羧酯酶抑制剂的用途。本发明还涉及含有这些化合物的药物组合物和杀虫剂制剂，以及治疗或改善给药后的毒性效应（如癌症治疗药物）、治疗或改善药物过量效应的方法，以及使用这些化合物提高杀虫剂和杀虫剂效力的方法。
• 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.
• 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：——
• Awdeenko A. P., Welitschko N. W., Zh. organ. khimii, 30 (1994) N 7, S 1042-1045
  作者：Awdeenko A. P., Welitschko N. W.

  DOI：——

  日期：——