methyl N-nosyl-p-aminobenzoate | 349398-11-4

• 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: methyl N-nosyl-p-aminobenzoate
• 英文别名: Methyl 4-(4-nitrobenzenesulfonamido)benzoate；methyl 4-[(4-nitrophenyl)sulfonylamino]benzoate
• CAS: 349398-11-4
• 化学式: C₁₄H₁₂N₂O₆S
• mdl: MFCD00705182
• 分子量: 336.325
• InChiKey: QHGUQTBMHZZNAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl N-nosyl-p-aminobenzoate 在 甲醇 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.5h， 生成 4-((4-nitrophenyl)sulfonamido)benzoic acid
  参考文献：
  名称：

  组织蛋白酶S的4-氨基呋喃-3-酮抑制剂的固相平行合成和SAR：磺酰胺P3取代基对效能和选择性的影响

  摘要：

  描述了组织蛋白酶S的高效和选择性的4-氨基呋喃-3-酮抑制剂。介绍了一系列在P3位置带有磺酰胺部分的抑制剂的合成及其构效关系。该系列的几个成员显示出对目标酶的亚纳摩尔抑制作用以及出色的选择性和良好的细胞效能。最有趣的抑制剂的分子模型描述了扩展S3口袋中的相互作用，并解释了观察到的对组织蛋白酶K的选择性。

  DOI：

  10.1016/j.bmc.2008.12.020
• 作为产物：
  描述：

  对氨基苯甲酸 在 碳酸氢钠 、 乙酰氯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 13.17h， 生成 methyl N-nosyl-p-aminobenzoate
  参考文献：
  名称：

  Discovery of a series of small molecules as potent histone deacetylase inhibitors

  摘要：

  A series of small molecules were designed and synthesized based on our previous virtual screening approach, which was performed to discover potent histone deacetylase inhibitors (HDACIs) with novel structures. The derived compounds were tested by Hela cell nucleus extract for enzyme inhibition assay. Tumor cell growth inhibition assays were performed using a series of tumor cell lines. Molecule 4h has the best performance among these compounds with enzyme inhibition IC50 of 0.14 mu M and tumor cell growth inhibition IC50 of 1.85 (U937), 2.02 (HL60), 2.67 (K562). Docking studies showed that multiple H-bonds and hydrophobic interactions make 4h binding to the active site of HDAC. 4h has the advantage of low molecular weight, so a variety of structural modifications can be performed in our further studies.

  DOI：

  10.3109/14756366.2013.780237

文献信息

• Highly specific N-monomethylation of primary aromatic amines
  作者：Adolfo Le Pera、Antonella Leggio、Angelo Liguori

  DOI：10.1016/j.tet.2006.03.104

  日期：2006.6

  A synthetic methodology for the specific conversion of primary aromatic amines into their N-monomethyl derivatives under very mild conditions is presented. Anilines are treated with 4-nitrobenzenesulfonyl (nosyl) chloride to generate the corresponding sulfonamides 2 in high yields. The subsequent N-methylation reaction of the sulfonamides 2 with a solution of diazomethane is rapid and quantitative

  提出了一种在非常温和的条件下将芳族伯胺具体转化为N-单甲基衍生物的合成方法。用4-硝基苯磺酰（壬基）氯化物处理苯胺，以高产率产生相应的磺酰胺2。磺酰胺2与重氮甲烷溶液的随后N-甲基化反应是快速且定量的。使用试剂体系巯基乙酸/ 1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU）可以轻松进行烷基保护基的除去，得到N-单甲基化的芳族胺4。该程序方便，高效，并产生了N-一甲基苯胺。
• Inhibitors of Histone Deacetylase
  申请人：Chakravarty K. Prasun

  公开号：US20080015190A1

  公开（公告）日：2008-01-17

  The present invention relates to hydroxamic acid derivatives that are inhibitors of histone deacetylase (HDAC). The compounds of the present invention are useful for treating cellular proliferative diseases, including cancer. Further, the compounds of the present invention are useful for treating neurodegenerative diseases, schizophrenia and stroke among other diseases. Further, the compounds of the present invention have antiprotozoal properties.

  本发明涉及羟羧酰胺酸衍生物，这些衍生物是组蛋白去乙酰化酶（HDAC）的抑制剂。本发明的化合物可用于治疗细胞增殖性疾病，包括癌症。此外，本发明的化合物可用于治疗神经退行性疾病、精神分裂症和中风等其他疾病。此外，本发明的化合物具有抗原虫特性。
• Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators
  作者：Jih-Hwa Guh、Wei-Ling Chang、Jian Yang、Su-Lin Lee、Shuo Wei、Dasheng Wang、Samuel K. Kulp、Ching-Shih Chen

  DOI：10.1021/jm901773d

  日期：2010.3.25

  proliferator-activated receptor (PPAR)gamma-independent activation of adenosine monophosphate-activated protein kinase (AMPK) and suppression of interleukin (IL)-6 production, we conducted a screening of an in-house, thiazolidinedione-based focused compound library to identify novel agents with these dual pharmacological activities. Cell-based assays pertinent to the activation status of AMPK and mammalian homologue

  鉴于噻唑烷二酮类化合物介导过氧化物酶体增殖物激活受体（PPAR）γ依赖性的腺苷单磷酸激活蛋白激酶（AMPK）激活和白介素（IL）-6产生抑制的独特能力，我们进行了筛选内部基于噻唑烷二酮的聚焦化合物库，以鉴定具有这些双重药理活性的新型药物。与AMPK的激活状态和雷帕霉素靶标的哺乳动物同源性有关的基于细胞的测定（即分别使AMPK和p70核糖体蛋白S6激酶磷酸化）和IL-6 / IL-6受体信号转导（即IL-6产生） （分别是脂多糖（LPS）刺激的THP-1人巨噬细胞中的信号转导和转录3磷酸化的激活剂）来筛选该化合物库，从而鉴定了化合物53（N- 4- [3-（1-甲基-环己基甲基）-2,4-二氧代-噻唑烷丁-5-亚甲基-甲基]-苯基] -4-硝基-3-三氟甲基苯磺酰胺）作为先导剂。有证据表明，这种药物诱导的LPS刺激的IL-6产生的抑制作用可归因于AMPK激活。此外，在C-26结肠腺癌细胞中
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：MERCK & CO INC

  公开号：WO2006017214A2

  公开（公告）日：2006-02-16

  The present invention relates to hydroxamic acid derivatives that are inhibitors of histone deacetylase (HDAC). The compounds of the present invention are useful for treating cellular proliferative diseases, including cancer. Further, the compounds of the present invention are useful for treating neurodegenerative diseases, schizophrenia and stroke among other diseases. Further, the compounds of the present invention have antiprotozoal properties.
• Discovery of a series of small molecules as potent histone deacetylase inhibitors
  作者：Lei Zhang、Xuejian Wang、Xiaoguang Li、Wenfang Xu

  DOI：10.3109/14756366.2013.780237

  日期：2014.6.1

  A series of small molecules were designed and synthesized based on our previous virtual screening approach, which was performed to discover potent histone deacetylase inhibitors (HDACIs) with novel structures. The derived compounds were tested by Hela cell nucleus extract for enzyme inhibition assay. Tumor cell growth inhibition assays were performed using a series of tumor cell lines. Molecule 4h has the best performance among these compounds with enzyme inhibition IC50 of 0.14 mu M and tumor cell growth inhibition IC50 of 1.85 (U937), 2.02 (HL60), 2.67 (K562). Docking studies showed that multiple H-bonds and hydrophobic interactions make 4h binding to the active site of HDAC. 4h has the advantage of low molecular weight, so a variety of structural modifications can be performed in our further studies.