1-((3-nitrophenyl)sulfonyl)-1H-indole-3-carbaldehyde | 367931-28-0

• 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: 1-((3-nitrophenyl)sulfonyl)-1H-indole-3-carbaldehyde
• 英文别名: 1-(3-nitrophenyl)sulfonylindole-3-carbaldehyde
• CAS: 367931-28-0
• 化学式: C₁₅H₁₀N₂O₅S
• 分子量: 330.321
• InChiKey: HNHKBJDPOHIFGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-((3-nitrophenyl)sulfonyl)-1H-indole-3-carbaldehyde 在 sodium chlorite 、 氨基磺酸 作用下， 以 水 、 叔丁醇 为溶剂， 反应 2.0h， 生成 1-((3-nitrophenyl)sulfonyl)-1H-indole-3-carboxylic acid
  参考文献：
  名称：

  Discovery of Small-Molecule Inhibitors of Receptor Activator of Nuclear Factor-κB Ligand with a Superior Therapeutic Index

  摘要：

  Receptor activator of nuclear factor-κB ligand (RANKL) constitutes the master mediator of osteoclastogenesis, while its pharmaceutical inhibition by a monoclonal antibody has been approved for the treatment of postmenopausal osteoporosis. To date, the pursuit of pharmacologically more favorable approaches using low-molecular-weight inhibitors has been hampered by low specificity and high toxicity issues. This study aimed to discover small-molecule inhibitors targeting RANKL trimer formation. Through a systematic screening of 39 analogues of SPD-304, a dual inhibitor of tumor necrosis factor (TNF) and RANKL trimerization, we identified four compounds (1b, 3b, 4a, and 4c) that selectively inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, without affecting TNF activity or osteoblast differentiation. Based on structure-activity observations extracted from the most potent and less toxic inhibitors of RANKL-induced osteoclastogenesis, we synthesized a focused set of compounds that revealed three potent inhibitors (19a, 19b, and 20a) with remarkably low cell-toxicity and improved therapeutic indexes as shown by the LC₅₀ to IC₅₀ ratio. These RANKL-selective inhibitors are an excellent starting point for the development of small-molecule therapeutics against osteolytic diseases.

  DOI：

  10.1021/acs.jmedchem.0c01316
• 作为产物：
  描述：

  3-硝基苯磺酰氯 在 potassium hydroxide 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 6.25h， 生成 1-((3-nitrophenyl)sulfonyl)-1H-indole-3-carbaldehyde
  参考文献：
  名称：

  Discovery of Small-Molecule Inhibitors of Receptor Activator of Nuclear Factor-κB Ligand with a Superior Therapeutic Index

  摘要：

  Receptor activator of nuclear factor-κB ligand (RANKL) constitutes the master mediator of osteoclastogenesis, while its pharmaceutical inhibition by a monoclonal antibody has been approved for the treatment of postmenopausal osteoporosis. To date, the pursuit of pharmacologically more favorable approaches using low-molecular-weight inhibitors has been hampered by low specificity and high toxicity issues. This study aimed to discover small-molecule inhibitors targeting RANKL trimer formation. Through a systematic screening of 39 analogues of SPD-304, a dual inhibitor of tumor necrosis factor (TNF) and RANKL trimerization, we identified four compounds (1b, 3b, 4a, and 4c) that selectively inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, without affecting TNF activity or osteoblast differentiation. Based on structure-activity observations extracted from the most potent and less toxic inhibitors of RANKL-induced osteoclastogenesis, we synthesized a focused set of compounds that revealed three potent inhibitors (19a, 19b, and 20a) with remarkably low cell-toxicity and improved therapeutic indexes as shown by the LC₅₀ to IC₅₀ ratio. These RANKL-selective inhibitors are an excellent starting point for the development of small-molecule therapeutics against osteolytic diseases.

  DOI：

  10.1021/acs.jmedchem.0c01316

文献信息

• Synthesis and Quantitative Structure–Activity Relationship (QSAR) Study of Novel <i>N</i>-Arylsulfonyl-3-acylindole Arylcarbonyl Hydrazone Derivatives as Nematicidal Agents
  作者：Zhiping Che、Shaoyong Zhang、Yonghua Shao、Lingling Fan、Hui Xu、Xiang Yu、Xiaoyan Zhi、Xiaojun Yao、Rui Zhang

  DOI：10.1021/jf400536q

  日期：2013.6.19

  natural-product-based pesticidal agents, 54 novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives were prepared, and their structures were well characterized by 1H NMR, 13C NMR, HRMS, ESI-MS, and mp. Their nematicidal activity was evaluated against that of the pine wood nematode, Bursaphelenchus xylophilus in vivo. Among all of the derivatives, especially V-12 and V-39 displayed the best

  在我们旨在发现和开发基于天然产物的杀虫剂的程序的继续中，制备了54种新颖的N-芳基磺酰基-3-酰基亚芳基芳基羰基hydr衍生物，并通过1 H NMR，13 C NMR对其结构进行了很好的表征， HRMS，ESI-MS和mp。在体内对它们的杀线虫活性针对松木线虫Bursaphelenchus xylophilus进行了评估。在所有衍生物中，尤其是V-12和V-39表现出最有希望的杀线虫活性，LC 50值分别为1.0969和1.2632 mg / L。这建议引入R 1和R 2为了进一步制备这些作为杀线虫剂的化合物，可以考虑将R 3作为吸电子取代基，R 3作为甲基，R 4作为苯基作为具有吸电子取代基的化合物。六个选定的描述符是WHIM描述符（E1m），两个GETAWAY描述符（R1m +和R3m +），负担特征值描述符（BEHm8）和两个边缘邻接索引描述符（EEig05x和EEig13d）。定量
• Synthesis of New 2-(N-Arylsulfonylindol-3-yl)-3-aryl-1,3-thiazolidin-4-ones as HIV-1 Inhibitors In Vitro
  作者：Rui-Ge Yang、Liu-Meng Yang、Ya-Zhen Ke、Ning Huang、Rui Zhang、Yong-Tang Zheng、Hui Xu

  DOI：10.2174/157018012799859936

  日期：2012.4.26

  Twenty-one 2-(N-arylsulfonylindol-3-yl)-3-aryl-1,3-thiazolidin-4-ones (4a-u) were synthesized and evaluated as HIV-1 inhibitors in vitro. Among all compounds, compounds 4n and 4p displayed the potent anti-HIV-1 activities with EC50 values of 3.48 and 8.61 μg/mL, and TI values of 34.08 and 23.22, respectively. It demonstrated that, to a series of 2-(N-arylsulfonyl-6-methylindol-3-yl)-3-aryl-1,3-thiazolidin-4-one derivatives, introduction of R2 as 4-Cl and R3 as H or 3-Cl could afford the more promising and potent compounds.

  合成了21个2-(N-芳基磺酰基吲哚-3-基)-3-芳基-1,3-噻唑烷-4-酮（4a-u），并对其进行了体外抗HIV-1活性评价。在所有化合物中，化合物4n和4p表现出了较强的抗HIV-1活性，其EC50值分别为3.48和8.61 μg/mL，治疗指数（TI）分别为34.08和23.22。研究表明，在一系列的2-(N-芳基磺酰基-6-甲基吲哚-3-基)-3-芳基-1,3-噻唑烷-4-酮衍生物中，引入R2为4-氯，R3为氢或3-氯可获得更具潜力的强效化合物。
• Antifungal agents. Part 5: Synthesis and antifungal activities of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles
  作者：Hui Xu、Yang-Yang Wang

  DOI：10.1016/j.bmcl.2010.10.084

  日期：2010.12

  In order to discover more promising antifungal agents, a series of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles (5a–r) were prepared and evaluated in vitro for their antifungal activities against seven phytopathogenic fungi. Especially compounds 5n and 5o exhibited more potent antifungal activities than or comparable to hymexazol, a commercially available agricultural fungicide at the

  为了发现更多有希望的抗真菌剂，制备了一系列N-芳基磺酰基-3-酰基林多酚（5a - r）的氨基胍衍生物，并在体外评估了其对7种植物病原真菌的抗真菌活性。尤其是化合物5n和5o表现出比Hymexazol更强的抗真菌活性，Hymexazol是浓度为100μg/ mL的市售农业杀菌剂。初步的结构-活性关系研究表明，引入了给电子性取代基R 1和R 2以及适当长度的取代基R 3 通常对于它们的抗真菌活性非常重要。