N,N′-(1,4-phenylene)bis(4-methoxybenzenesulfonamide)

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N′-(1,4-phenylene)bis(4-methoxybenzenesulfonamide)
• 英文别名: N,N'-(1,4-phenylene)bis(4-methoxybenzenesulfonamide)；Cambridge id 5528073；4-methoxy-N-[4-[(4-methoxyphenyl)sulfonylamino]phenyl]benzenesulfonamide
• 化学式: C₂₀H₂₀N₂O₆S₂
• 分子量: 448.521
• InChiKey: GTIPSFWDUFHOOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N′-(1,4-phenylene)bis(4-methoxybenzenesulfonamide) 在 (S)-3,3'-双(9-蒽基)-1,1'-联萘-2,2'-二基磷酸氢酯 、 lead(IV) tetraacetate 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 18.17h， 生成 N-(2-(tert-butyl)-1H-indol-3-yl)-4-methoxy-N-(4-((4-methoxyphenyl)sulfonamido)phenyl)benzenesulfonamide
  参考文献：
  名称：

  吲哚的催化选择性亲电胺化

  摘要：

  报道了手性磷酸（CPA）催化的吲哚选择性亲电胺化。该反应通过不对称的 1,6-加成与对醌二亚胺进行，以良好的收率和优异的 ee 值提供非手性N-磺酰基-3-芳基氨基吲哚。

  DOI：

  10.1002/anie.202205159
• 作为产物：
  描述：

  4-硝基苯胺 在 吡啶 、 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 N,N′-(1,4-phenylene)bis(4-methoxybenzenesulfonamide)
  参考文献：
  名称：

  Structure–Activity and Structure–Property Relationship and Exploratory in Vivo Evaluation of the Nanomolar Keap1–Nrf2 Protein–Protein Interaction Inhibitor

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00185

文献信息

• Design, synthesis and evaluation of novel small molecules acting as Keap1-Nrf2 protein-protein interaction inhibitors
  作者：Yunfeng Sun、Lulu Zheng、Bo Yang、Shuyu Ge、Qiang Li、Mingwan Zhang、Shenghui Shen、Yin Ying

  DOI：10.1080/14756366.2022.2124408

  日期：2022.12.31

  Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has recently been introduced as an attractive approach to control life-threatening diseases like myocarditis. The present study aimed to investigate the potential application in myocarditis of a series of novel non-naphthalene derivatives as potential Keap1-Nrf2 PPI inhibitors. Our results indicated that the optimal compound

  摘要 最近引入了直接干扰 Kelch 样 ECH 相关蛋白 1 (Keap1)-Nrf2 蛋白-蛋白相互作用 (PPI) 作为一种有吸引力的方法来控制心肌炎等危及生命的疾病。本研究旨在探讨一系列新型非萘衍生物作为潜在的 Keap1-Nrf2 PPI 抑制剂在心肌炎中的潜在应用。我们的结果表明，最佳化合物K22表现出最高的代谢稳定性，并在体外显示出显着的 Keap1-Nrf2 PPI 抑制活性。K22有效触发 Nrf2 激活并增加 H9c2 细胞中 Nrf2 调节基因的蛋白质和 mRNA 表达。此外，用K22进行预处理显示可减轻 LPS 诱导的 H9c2 细胞损伤，导致炎症因子和活性氧 (ROS) 水平显着降低。此外，在 Ames 试验中， K22也被证明是非诱变的。总体而言，我们的研究结果表明，K22作为 Keap1-Nrf2 PPI 抑制剂可能是一种有前途的药物先导药物，用于治疗心肌炎。
• Zinc Trifluoromethanesulfonate-Catalyzed <i>para</i>-Selective Amination of Free Anilines and Free Phenols with Quinoneimides
  作者：Weiqiao Lan、Jiatong Zhu、Buweihailiqiemu Abulaiti、Genyuan Chen、Zhihao Zhang、Nan Yan、Jie-Ping Wan、Xiaomei Zhang、Lihua Liao

  DOI：10.1021/acs.joc.2c01600

  日期：2022.11.4

  An efficient zinc-catalyzed amination of free anilines and free phenols with quinoneimides has been disclosed, which proceeds smoothly under simple and mild conditions. The para-selective amination is accomplished on the anilines and phenols via a 1,6-addition pathway, leading to C–N bond formation. The developed protocol offers a promising approach not only for the construction of structurally diverse

  已公开了一种有效的锌催化游离苯胺和游离酚与醌酰亚胺的胺化反应，该反应在简单温和的条件下顺利进行。苯胺和苯酚通过 1,6-加成途径完成对位选择性胺化，从而形成 C-N键。所开发的协议不仅为构建结构多样的对苯二胺化合物提供了一种很有前景的方法，而且收率很高，而且还为游离苯酚衍生物的对胺化合成提供了良好的收率。该协议还扩展了涉及 quinoneimide 的 1,6-加成反应的应用。
• 1,6‐Addition Reactions of Difluoroenol Silyl Ethers with Benzoquinones and Quinonediimines To Access Difluorooxymethyl and Difluoroaminomethyl Compounds
  作者：Peng Hong、Jinjing Xu、Jinshan Li、Xiaolei Zhu、Anguo Ying、Zhiming Wang、Jianguo Yang

  DOI：10.1002/adsc.202300877

  日期：2023.12.19

  The etherification and amination of difluoroenol silyl ethers with benzoquinones and quinonediimines were achieved by using hexafluoroisopropanol (HFIP) as the solvent. This 1,6-addition reaction could construct difluorooxymethyl and difluoroaminomethyl compounds under metal-free conditions. It is preliminarily speculated that the reaction took place through a single electron transfer (SET) process

  以六氟异丙醇（HFIP）为溶剂，实现了二氟烯醇硅醚与苯醌和醌二亚胺的醚化和胺化反应。该1,6-加成反应可以在无金属条件下构建二氟羟甲基和二氟氨基甲基化合物。初步推测该反应是通过单电子转移（SET）过程发生的。
• Atroposelective Synthesis of <scp>2‐Arylindoles</scp> via Chiral Phosphoric <scp>Acid‐Catalyzed</scp> Direct Amination of Indoles^†
  作者：Wen Bao、Ye‐Hui Chen、Yu‐Wei Liu、Shao‐Hua Xiang、Bin Tan

  DOI：10.1002/cjoc.202300589

  日期：2024.4

  Indole-based atropisomers are a very important class of axially chiral compounds. However, the atroposelective synthesis of axially chiral 2-arylindole remains largely unexplored. In this study, we report the successful synthesis of atropisomeric 2-arylindoles using direct amination of indoles with p-quinonediimines in the presence of chiral phosphoric acid as a catalyst. Quinonediimine acts as an

  吲哚基阻转异构体是一类非常重要的轴向手性化合物。然而，轴向手性 2-芳基吲哚的逆向选择性合成在很大程度上仍未被探索。在这项研究中，我们报道了在手性磷酸作为催化剂存在下，使用对醌二亚胺直接胺化吲哚，成功合成了阻转异构体2-芳基吲哚。醌二亚胺通过亚胺的形式极性反转充当胺化试剂。发现 2-吲哚 2-芳基上的丙二酸基团对于产物的高对映选择性至关重要。这可能是由于酯基和催化剂之间的额外相互作用以及分子内氢键造成的。我们的研究结果为2-芳基吲哚阻转异构体的不对称构建提供了新策略。
• 10.1021/acs.orglett.4c01441
  作者：Subba, Parbat、Sahoo, Sushree Ranjan、Khajuria, Chhavi、Singh, Vinod K.

  DOI：10.1021/acs.orglett.4c01441

  日期：——

  first use of p-quinone diimide for the aminative dearomatization of 2,3-disubstituted indoles to furnish C3 aza-quaternary chiral indolenines. This approach, which proceeds via an electrophilic 1,6-addition of p-quinone diimide, allows the synthesis of an array of optically active aza-quaternary indolenines with high yields and excellent enantioselectivities. A one-pot approach of the same has also been

  在此，我们报道了对醌二酰亚胺首次用于 2,3-二取代吲哚的氨基脱芳构化，以提供 C3 氮杂季手性吲哚。这种方法通过对醌二酰亚胺的亲电 1,6-加成进行，可以合成一系列具有高产率和优异对映选择性的光学活性氮杂季假吲哚。还建立了相同的一锅法，以进一步提高该协议的合成可及性。