N-(3,4-dimethylphenyl)-4-methoxybenzenesulfonamide | 329941-86-8

• 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-(3,4-dimethylphenyl)-4-methoxybenzenesulfonamide
• 英文别名: NCGC00187727
• CAS: 329941-86-8
• 化学式: C₁₅H₁₇NO₃S
• 分子量: 291.371
• InChiKey: UTYRQPFZVAGFJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(三甲基硅)苯基三氟甲烷磺酸盐 、 N-(3,4-dimethylphenyl)-4-methoxybenzenesulfonamide 在 cesium fluoride 作用下， 以 乙腈 为溶剂， 以86 %的产率得到N-(3,4-dimethylphenyl)-4-methoxy-N-phenylbenzenesulfonamide
  参考文献：
  名称：

  N,N‐Diarysulfonamide reduces proinflammatory cytokine interleukin‐6 levels in cells through nuclear factor‐κB regulation

  摘要：

  The synthesized sulfonamides were evaluated for cytotoxicity followed by the cytokine/inflammatory marker’s inhibition capability and its mechanism of action in RAW‐264.7 cells. Elevated interleukin‐6 (IL‐6) levels have been reported in inflammatory conditions and inflammation‐associated disorders. Hence, reducing the IL‐6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL‐6 levels in lipopolysaccharide (LPS) challenged RAW‐264.7 cells at 12.5 µM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL‐6 levels was found to be in the range of 9.7 to 2.6 µM. The promising compounds 5y (IC50 of 2.6 µM) and 5n (IC50 of 4.1 µM) along with other derivatives fulfil drug‐likeness parameters laid down by Lipinski’s rule of five. Further, analysis using RTqPCR and Western‐blot analysis revealed that treatment with 5n significantly reduced the expression of pro‐inflammatory, inflammatory and macrophage marker’s expression (IL‐1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that RL‐442 exhibited anti‐inflammatory properties by modulating the nuclear factor‐κB (NF‐κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.

  DOI：

  10.1002/cmdc.202300598
• 作为产物：
  描述：

  3,4-二甲基苯胺 、 对甲氧基苯磺酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以78 %的产率得到N-(3,4-dimethylphenyl)-4-methoxybenzenesulfonamide
  参考文献：
  名称：

  N,N‐Diarysulfonamide reduces proinflammatory cytokine interleukin‐6 levels in cells through nuclear factor‐κB regulation

  摘要：

  The synthesized sulfonamides were evaluated for cytotoxicity followed by the cytokine/inflammatory marker’s inhibition capability and its mechanism of action in RAW‐264.7 cells. Elevated interleukin‐6 (IL‐6) levels have been reported in inflammatory conditions and inflammation‐associated disorders. Hence, reducing the IL‐6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL‐6 levels in lipopolysaccharide (LPS) challenged RAW‐264.7 cells at 12.5 µM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL‐6 levels was found to be in the range of 9.7 to 2.6 µM. The promising compounds 5y (IC50 of 2.6 µM) and 5n (IC50 of 4.1 µM) along with other derivatives fulfil drug‐likeness parameters laid down by Lipinski’s rule of five. Further, analysis using RTqPCR and Western‐blot analysis revealed that treatment with 5n significantly reduced the expression of pro‐inflammatory, inflammatory and macrophage marker’s expression (IL‐1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that RL‐442 exhibited anti‐inflammatory properties by modulating the nuclear factor‐κB (NF‐κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.

  DOI：

  10.1002/cmdc.202300598

文献信息

• 3 Substituted N-(aryl- or heteroaryl)-pyrazolo[1,5-a]pyrimidines as Kinase Inhibitors
  申请人：Masuya Keiichi

  公开号：US20090275593A1

  公开（公告）日：2009-11-05

  The invention relates to 3-substituted N-(aryl- or heteroaryl)-pyrazolo[1,5-a]pyrimidine compounds, their use as kinase inhibitors, new pharmaceutical formulations comprising said compounds, said compounds for use in the diagnostic or therapeutic treatment of warm-blooded animals, especially humans, their use in the treatment of diseases or for the manufacture of pharmaceutical formulations useful in the treatment of diseases that respond to modulation of kinase, especially tie-2 kinase, activity, methods of treatment comprising administration of said compounds to a warm-blooded animal, especially a human, and processes for the manufacture of said compounds.

  本发明涉及3-取代N-(芳基或杂环芳基)-吡唑并[1,5-a]嘧啶化合物，它们作为激酶抑制剂的用途，包括所述化合物的新药物制剂，所述化合物用于温血动物，特别是人类的诊断或治疗治疗，它们用于治疗疾病或制造对于对激酶调节有响应的疾病的药物制剂，特别是Tie-2激酶活性，治疗方法包括向温血动物，特别是人类，给予所述化合物的给药，以及制造所述化合物的过程。
• 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase
  作者：Martin J. Walsh、Kyle R. Brimacombe、Henrike Veith、James M. Bougie、Thomas Daniel、William Leister、Lewis C. Cantley、William J. Israelsen、Matthew G. Vander Heiden、Min Shen、Douglas S. Auld、Craig J. Thomas、Matthew B. Boxer

  DOI：10.1016/j.bmcl.2011.08.114

  日期：2011.11

  Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation. Here we report the third chemotype in a series of PKM2 activators based on the 2-oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis, structure activity relationships, selectivity and notable physiochemical properties are described. Published by Elsevier Ltd.
• N,N‐Diarysulfonamide reduces proinflammatory cytokine interleukin‐6 levels in cells through nuclear factor‐κB regulation
  作者：Dattatraya Babar、Gopinath Khansole、Vishalkumar Singh、Akash Shinde、Vaishnavi Kambhampati、Sai Balaji Andugulapati、Haridas B. Rode

  DOI：10.1002/cmdc.202300598

  日期：——

  The synthesized sulfonamides were evaluated for cytotoxicity followed by the cytokine/inflammatory marker’s inhibition capability and its mechanism of action in RAW‐264.7 cells. Elevated interleukin‐6 (IL‐6) levels have been reported in inflammatory conditions and inflammation‐associated disorders. Hence, reducing the IL‐6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL‐6 levels in lipopolysaccharide (LPS) challenged RAW‐264.7 cells at 12.5 µM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL‐6 levels was found to be in the range of 9.7 to 2.6 µM. The promising compounds 5y (IC50 of 2.6 µM) and 5n (IC50 of 4.1 µM) along with other derivatives fulfil drug‐likeness parameters laid down by Lipinski’s rule of five. Further, analysis using RTqPCR and Western‐blot analysis revealed that treatment with 5n significantly reduced the expression of pro‐inflammatory, inflammatory and macrophage marker’s expression (IL‐1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that RL‐442 exhibited anti‐inflammatory properties by modulating the nuclear factor‐κB (NF‐κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.