(E)-N′-(4-fluorobenzylidene)-1H-indole-3-carbohydrazide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-N′-(4-fluorobenzylidene)-1H-indole-3-carbohydrazide
• 英文别名: N'-(4-fluorobenzylidene)-1H-indole-3-carbohydrazide；N-[(E)-(4-fluorophenyl)methylideneamino]-1H-indole-3-carboxamide
• 化学式: C₁₆H₁₂FN₃O
• 分子量: 281.289
• InChiKey: MJIULDHNIWSDFJ-DJKKODMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 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：
  57.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-N′-(4-fluorobenzylidene)-1H-indole-3-carbohydrazide 、 4-氯氯苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 以85%的产率得到(E)-1-(4-chlorobenzyl)-N'-(4-fluorobenzylidene)-1H-indole-3-carbohydrazide
  参考文献：
  名称：

  Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites

  摘要：

  The aim of this study was to design and synthesize COX-1/COX-2 balanced inhibitors incorporating the structural motifs of anti-inflammatory ascidian metabolites. We designed a series of substituted indole analogs that incorporate the key structures of the ascidian metabolites, herdmanines C and D. The synthesized analogs were tested for their inhibitory activity against COX-1 and COX-2, and compound 5m, which displayed balanced inhibition, was further evaluated for in vitro anti-inflammatory activity. Compound 5m suppressed the expression of pro-inflammatory factors, including iNOS, COX-2, TNF-alpha, and IL-6 in LPS-stimulated murine RAW264.7 macrophages. The reduction of PGE2, NO, and ROS was also observed, together with the suppression of NF-kappa B, IKK, and I kappa B alpha phosphorylation. Our results characterized 5m as a COX-1/COX-2 balanced inhibitor that subsequently caused ROS inhibition and NF-kappa B suppression, and culminated in the suppression of iNOS, COX-2, TNF-alpha, and IL-6 expression. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.016
• 作为产物：
  描述：

  3-吲哚甲酸 在 hydrazine hydrate 、 硫酸 、 丙酸 作用下， 以 乙醇 为溶剂， 反应 28.5h， 生成 (E)-N′-(4-fluorobenzylidene)-1H-indole-3-carbohydrazide
  参考文献：
  名称：

  Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites

  摘要：

  The aim of this study was to design and synthesize COX-1/COX-2 balanced inhibitors incorporating the structural motifs of anti-inflammatory ascidian metabolites. We designed a series of substituted indole analogs that incorporate the key structures of the ascidian metabolites, herdmanines C and D. The synthesized analogs were tested for their inhibitory activity against COX-1 and COX-2, and compound 5m, which displayed balanced inhibition, was further evaluated for in vitro anti-inflammatory activity. Compound 5m suppressed the expression of pro-inflammatory factors, including iNOS, COX-2, TNF-alpha, and IL-6 in LPS-stimulated murine RAW264.7 macrophages. The reduction of PGE2, NO, and ROS was also observed, together with the suppression of NF-kappa B, IKK, and I kappa B alpha phosphorylation. Our results characterized 5m as a COX-1/COX-2 balanced inhibitor that subsequently caused ROS inhibition and NF-kappa B suppression, and culminated in the suppression of iNOS, COX-2, TNF-alpha, and IL-6 expression. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.016

文献信息

• Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus
  作者：Bin Liu、Rui Li、Yanan Li、Songyi Li、Jin Yu、Binfen Zhao、Ancai Liao、Ying Wang、Ziwen Wang、Aidang Lu、Yuxiu Liu、Qingmin Wang

  DOI：10.1021/acs.jafc.8b06175

  日期：2019.2.20

  foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a–9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.

  植物病毒性疾病导致农作物产量和质量大幅下降。天然产物一直是药用和农业化学中铅发现的宝贵来源。制备了一系列嘧啶碱生物碱及其衍生物，并通过核磁共振（NMR）光谱和高分辨率质谱（HR-MS）进行了鉴定。首次系统地研究了这些生物碱对烟草花叶病毒（TMV）的抗病毒活性。大多数化合物显示出比利巴韦林更高的抗病毒活性。化合物5l，9h和10h具有比宁南霉素（也许是目前使用最广泛的抗病毒药）相似或更高的抗病毒活性，已成为新的抗病毒先导化合物。这项系统的结构-活性-关系研究为简化这些生物碱的结构奠定了基础。还发现开环产物酰基hydr 9a - 9u具有良好的抗病毒活性。此外，所有合成的化合物均表现出广谱杀真菌活性。该研究为吡皮氨酸生物碱作为新型抗病毒药物的研究和开发提供了重要的信息。
• Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites
  作者：Zhiran Ju、Mingzhi Su、Jongki Hong、Eun La Kim、Hyung Ryong Moon、Hae Young Chung、Suhkmann Kim、Jee H. Jung

  DOI：10.1016/j.ejmech.2019.07.016

  日期：2019.10

  The aim of this study was to design and synthesize COX-1/COX-2 balanced inhibitors incorporating the structural motifs of anti-inflammatory ascidian metabolites. We designed a series of substituted indole analogs that incorporate the key structures of the ascidian metabolites, herdmanines C and D. The synthesized analogs were tested for their inhibitory activity against COX-1 and COX-2, and compound 5m, which displayed balanced inhibition, was further evaluated for in vitro anti-inflammatory activity. Compound 5m suppressed the expression of pro-inflammatory factors, including iNOS, COX-2, TNF-alpha, and IL-6 in LPS-stimulated murine RAW264.7 macrophages. The reduction of PGE2, NO, and ROS was also observed, together with the suppression of NF-kappa B, IKK, and I kappa B alpha phosphorylation. Our results characterized 5m as a COX-1/COX-2 balanced inhibitor that subsequently caused ROS inhibition and NF-kappa B suppression, and culminated in the suppression of iNOS, COX-2, TNF-alpha, and IL-6 expression. (C) 2019 Elsevier Masson SAS. All rights reserved.