(S)-ethyl 6-chloro-3-(3,7-dimethyloctanoyl)-1H-indole-2-carboxylate

• 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: (S)-ethyl 6-chloro-3-(3,7-dimethyloctanoyl)-1H-indole-2-carboxylate
• 英文别名: N247；Eleftheriaidis-14d；ethyl 6-chloro-3-[(3S)-3,7-dimethyloctanoyl]-1H-indole-2-carboxylate
• 化学式: C₂₁H₂₈ClNO₃
• 分子量: 377.911
• InChiKey: UMWSDKOJAYNGGO-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-ethyl 6-chloro-3-(3,7-dimethyloctanoyl)-1H-indole-2-carboxylate 在 lithium hydroxide trihydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 C₁₉H₂₄ClNO₃
  参考文献：
  名称：

  Novel 15-Lipoxygenase-1 Inhibitor Protects Macrophages from Lipopolysaccharide-Induced Cytotoxicity

  摘要：

  Various mechanisms for regulated cell death include the formation of oxidative mediators such as lipid peroxides and nitric oxide (NO). In this respect, 15-lipoxygenase-1 (15-LOX-1) is a key enzyme that catalyzes the formation of lipid peroxides. The actions of these peroxides are interconnected with nuclear factor-?B signaling and NO production. Inhibition of 15-LOX-1 holds promise to interfere with regulated cell death in inflammatory conditions. In this study, a novel potent 15-LOX-1 inhibitor, 9c (i472), was developed and structure-activity relationships were explored. In vitro, this inhibitor protected cells from lipopolysaccharide-induced cell death, inhibiting NO formation and lipid peroxidation. Thus, we provide a novel 15-LOX-1 inhibitor that inhibits cellular NO production and lipid peroxidation, which set the stage for further exploration of these mechanisms.

  DOI：

  10.1021/acs.jmedchem.9b00212
• 作为产物：
  描述：

  (S)-(-)-香茅酸 在 草酰氯 、 palladium on activated charcoal 、 氢气 、 四氯化锡 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (S)-ethyl 6-chloro-3-(3,7-dimethyloctanoyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  具有体外和离体抗炎特性的强效 15-脂氧合酶 1 抑制剂的合理开发

  摘要：

  人 15-脂氧合酶-1 (h-15-LOX-1) 是哺乳动物的脂氧合酶，在哮喘、慢性阻塞性肺病和慢性支气管炎等多种炎症性肺病中起重要作用。需要新的强效 h-15-LOX-1 抑制剂来进一步探索这种酶的作用并进行药物发现工作。在这项研究中，我们采用了一种方法，我们筛选了一个片段集合，该片段集合专注于含氮杂环的多样化取代模式，如吲哚、喹诺酮类、吡唑类等。我们将这种方法称为面向替代的片段筛选 (SOS)，因为它侧重于识别新的替代模式而不是新的支架。这种方法能够识别对 h-1-5-LOX-1 抑制具有良好效力和清晰结构-活性关系 (SAR) 的命中。14d以 36 nM的K i与酶结合。我们最好的抑制剂的体外和离体生物学评估表明白细胞介素 10 (IL-10) 基因表达显着增加，这表明其具有抗炎特性。

  DOI：

  10.1021/acs.jmedchem.5b01121

文献信息

• Rational Development of a Potent 15-Lipoxygenase-1 Inhibitor with <i>in Vitro</i> and <i>ex Vivo</i> Anti-inflammatory Properties
  作者：Nikolaos Eleftheriadis、Constantinos G. Neochoritis、Niek G. J. Leus、Petra E. van der Wouden、Alexander Dömling、Frank J. Dekker

  DOI：10.1021/acs.jmedchem.5b01121

  日期：2015.10.8

  potent inhibitors of h-15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery efforts. In this study, we applied an approach in which we screened a fragment collection that is focused on a diverse substitution pattern of nitrogen-containing heterocycles such as indoles, quinolones, pyrazoles, and others. We denoted this approach substitution-oriented fragment screening

  人 15-脂氧合酶-1 (h-15-LOX-1) 是哺乳动物的脂氧合酶，在哮喘、慢性阻塞性肺病和慢性支气管炎等多种炎症性肺病中起重要作用。需要新的强效 h-15-LOX-1 抑制剂来进一步探索这种酶的作用并进行药物发现工作。在这项研究中，我们采用了一种方法，我们筛选了一个片段集合，该片段集合专注于含氮杂环的多样化取代模式，如吲哚、喹诺酮类、吡唑类等。我们将这种方法称为面向替代的片段筛选 (SOS)，因为它侧重于识别新的替代模式而不是新的支架。这种方法能够识别对 h-1-5-LOX-1 抑制具有良好效力和清晰结构-活性关系 (SAR) 的命中。14d以 36 nM的K i与酶结合。我们最好的抑制剂的体外和离体生物学评估表明白细胞介素 10 (IL-10) 基因表达显着增加，这表明其具有抗炎特性。
• Novel 15-Lipoxygenase-1 Inhibitor Protects Macrophages from Lipopolysaccharide-Induced Cytotoxicity
  作者：Hao Guo、Iris C. Verhoek、Gerian G. H. Prins、Ramon van der Vlag、Petra E. van der Wouden、Ronald van Merkerk、Wim J. Quax、Peter Olinga、Anna K. H. Hirsch、Frank J. Dekker

  DOI：10.1021/acs.jmedchem.9b00212

  日期：2019.5.9

  Various mechanisms for regulated cell death include the formation of oxidative mediators such as lipid peroxides and nitric oxide (NO). In this respect, 15-lipoxygenase-1 (15-LOX-1) is a key enzyme that catalyzes the formation of lipid peroxides. The actions of these peroxides are interconnected with nuclear factor-?B signaling and NO production. Inhibition of 15-LOX-1 holds promise to interfere with regulated cell death in inflammatory conditions. In this study, a novel potent 15-LOX-1 inhibitor, 9c (i472), was developed and structure-activity relationships were explored. In vitro, this inhibitor protected cells from lipopolysaccharide-induced cell death, inhibiting NO formation and lipid peroxidation. Thus, we provide a novel 15-LOX-1 inhibitor that inhibits cellular NO production and lipid peroxidation, which set the stage for further exploration of these mechanisms.