N,N'-(naphthalene-1,4-diyl)bis(3-trifluoromethylbenzenesulfonamide) | 1809564-53-1

• 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(3-trifluoromethylbenzenesulfonamide)
• 英文别名: Benzenesulfonamide, N,Na(2)-1,4-naphthalenediylbis[3-(trifluoromethyl)-；3-(trifluoromethyl)-N-[4-[[3-(trifluoromethyl)phenyl]sulfonylamino]naphthalen-1-yl]benzenesulfonamide
• CAS: 1809564-53-1
• 化学式: C₂₄H₁₆F₆N₂O₄S₂
• 分子量: 574.524
• InChiKey: ANLICNXTTKOSON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1,4-diaminonaphthalene hydrochloride salt 、 3-三氟甲基苯磺酰氯 在 吡啶 作用下， 反应 24.0h， 以50%的产率得到N,N'-(naphthalene-1,4-diyl)bis(3-trifluoromethylbenzenesulfonamide)
  参考文献：
  名称：

  Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.08.049

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.