N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide | 1245747-31-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide
• 英文别名: N,N'-bis(4-cyano-2-phenylpyrazol-3-yl)oxamide
• CAS: 1245747-31-2
• 化学式: C₂₂H₁₄N₈O₂
• 分子量: 422.406
• InChiKey: BTUMJTVAZKCRBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide 、 二环己胺 以 四氢呋喃 为溶剂， 反应 2.0h， 以63%的产率得到
  参考文献：
  名称：

  Synthesis and Evaluation of Novel Pyrazole Ethandiamide Compounds as Inhibitors of Human THP-1 Monocytic Cell Neurotoxicity

  摘要：

  神经炎症和微胶质细胞介导的神经毒性有助于多种神经退行性疾病的发病机制；因此，识别能够抑制胶质细胞不良激活的新化合物是一个重要目标。我们先前已经鉴定出一类三取代吡唑酮具有神经保护和抗炎性质的化合物。在这里，我们描述了第二代吡唑酮类似物，旨在改善它们在炎症条件下对神经元的神经保护活性。设计了吡唑基草酰胺衍生物来探索立体和电子因素的影响。进行了三种体外实验来评估这些化合物在人类THP-1、PC-3和SH-SY5Y细胞中的抗神经毒性、神经保护和细胞毒性活性。五种化合物显著减少了免疫刺激的微胶质细胞样人类THP-1单核细胞释放的神经毒性物质。其中一种化合物还被发现在暴露于细胞毒性THP-1细胞上清液时保护SH-SY5Y神经元细胞。尽管其中一种类似物由于干扰细胞存活率分析而被舍弃，但大多数化合物在使用的浓度下对培养细胞无害（1-100 μM）。本文报道的新化合物为未来开发作为神经炎症和神经保护药物新型抑制剂的先导候选药物提供了设计模板。

  DOI：

  10.3390/cells8070655
• 作为产物：
  描述：

  草酰氯 、 5-氨基-1-苯基吡唑-4-腈 以 四氢呋喃 为溶剂， 反应 24.5h， 以85%的产率得到N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pyrazole compounds

  摘要：

  A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d] pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.018

文献信息

• Synthesis and Evaluation of Novel Pyrazole Ethandiamide Compounds as Inhibitors of Human THP-1 Monocytic Cell Neurotoxicity
  作者：Jordan A. McKenzie、Reham F. Barghash、Azhaar T. Alsaggaf、Omkar Kulkarni、Kalun Boudreau、Frederic Menard、Edward G. Neeland、Andis Klegeris

  DOI：10.3390/cells8070655

  日期：——

  Neuroinflammation and microglia-mediated neurotoxicity contribute to the pathogenesis of a broad range of neurodegenerative diseases; therefore, identifying novel compounds that can suppress adverse activation of glia is an important goal. We have previously identified a class of trisubstituted pyrazoles that possess neuroprotective and anti-inflammatory properties. Here, we describe a second generation of pyrazole analogs that were designed to improve their neuroprotective activity toward neurons under inflammatory conditions. Pyrazolyl oxalamide derivatives were designed to explore the effects of steric and electronic factors. Three in vitro assays were performed to evaluate the compounds’ anti-neurotoxic, neuroprotective, and cytotoxic activity using human THP-1, PC-3, and SH-SY5Y cells. Five compounds significantly reduced the neurotoxic secretions from immune-stimulated microglia-like human THP-1 monocytic cells. One of these compounds was also found to protect SH-SY5Y neuronal cells when they were exposed to cytotoxic THP-1 cell supernatants. While one of the analogs was discarded due to its interference with the cell viability assay, most compounds were innocuous to the cultured cells at the concentrations used (1–100 μM). The new compounds reported herein provide a design template for the future development of lead candidates as novel inhibitors of neuroinflammation and neuroprotective drugs.

  神经炎症和微胶质细胞介导的神经毒性有助于多种神经退行性疾病的发病机制；因此，识别能够抑制胶质细胞不良激活的新化合物是一个重要目标。我们先前已经鉴定出一类三取代吡唑酮具有神经保护和抗炎性质的化合物。在这里，我们描述了第二代吡唑酮类似物，旨在改善它们在炎症条件下对神经元的神经保护活性。设计了吡唑基草酰胺衍生物来探索立体和电子因素的影响。进行了三种体外实验来评估这些化合物在人类THP-1、PC-3和SH-SY5Y细胞中的抗神经毒性、神经保护和细胞毒性活性。五种化合物显著减少了免疫刺激的微胶质细胞样人类THP-1单核细胞释放的神经毒性物质。其中一种化合物还被发现在暴露于细胞毒性THP-1细胞上清液时保护SH-SY5Y神经元细胞。尽管其中一种类似物由于干扰细胞存活率分析而被舍弃，但大多数化合物在使用的浓度下对培养细胞无害（1-100 μM）。本文报道的新化合物为未来开发作为神经炎症和神经保护药物新型抑制剂的先导候选药物提供了设计模板。
• Synthesis and biological evaluation of novel pyrazole compounds
  作者：Amal M. Youssef、Edward G. Neeland、Erika B. Villanueva、M. Sydney White、Ibrahim M. El-Ashmawy、Brian Patrick、Andis Klegeris、Alaa S. Abd-El-Aziz

  DOI：10.1016/j.bmc.2010.06.018

  日期：2010.8

  A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d] pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2. (C) 2010 Elsevier Ltd. All rights reserved.