(2S,4aS,6aR,6bS,8aR,12aS,14bR)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxylic acid | 1402570-92-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,4aS,6aR,6bS,8aR,12aS,14bR)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxylic acid
• CAS: 1402570-92-6
• 化学式: C₃₁H₄₁NO₃
• 分子量: 475.671
• InChiKey: JRQQUGPXPNIOAJ-WSOBQERESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  35
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  甘草次酸 在 吡啶 、 盐酸 、 sodium tetrahydroborate 、 碘 、 potassium carbonate 、 sodium hydroxide 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 82.0h， 生成 (2S,4aS,6aR,6bS,8aR,12aS,14bR)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxylic acid
  参考文献：
  名称：

  Discovery of a Potential Anti-Inflammatory Agent: 3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile

  摘要：

  Fifteen novel derivatives of glycyrrhetinic acid (GA) were synthesized and evaluated for anti-inflammatory activities. It was found that the introduction of 1-en-3-one and 9(11),12-diene and 2,20-dinitrile functionalities into the scaffold of GA led to the discovery of potent compound 19 for inhibition of LPS-induced NO production. Furthermore, 19 effectively inhibited the protein and mRNA expression of inducible NO synthase (iNOS) and the mRNA expression of TNF-alpha, IL-6, and IL-1 beta in LPS-stimulated RAW 264.7 macrophages. Mechanistically, 19 exerted inhibitory effects on the activation of the three main MAPKs and phosphorylation and degradation of I kappa B-alpha, as well as the ratio of nuclear/cytosolic content of p65. Importantly, 19 significantly decreased the mortality rate in the mouse model of LPS-induced sepsis shock. It is noteworthy that inhibitory effect of 19 on NO production was not blocked by the glucocorticoid receptor antagonist mifepristone, indicating that it does not act through the glucocorticoid receptor.

  DOI：

  10.1021/jm301652t

文献信息

• Selective Inhibitors Of i-NOS For Use Against Viral Infection
  申请人：UCL Business PLC

  公开号：US20180214430A1

  公开（公告）日：2018-08-02

  The present invention concerns compounds for use in the prevention of viral replication and/or the prevention or treatment of a viral infection, wherein the compounds are selective inhibitors of inducible nitric oxide synthase, and methods of preventing viral replication and/or preventing or treating viral infections in a subject comprising administering a prophylactically or therapeutically effective amount of the compounds.
• Discovery of a Potential Anti-Inflammatory Agent: 3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile
  作者：Ran You、Wenyan Long、Zhonghui Lai、Lei Sha、Kai Wu、Xing Yu、Yisheng Lai、Hui Ji、Zhangjian Huang、Yihua Zhang

  DOI：10.1021/jm301652t

  日期：2013.3.14

  Fifteen novel derivatives of glycyrrhetinic acid (GA) were synthesized and evaluated for anti-inflammatory activities. It was found that the introduction of 1-en-3-one and 9(11),12-diene and 2,20-dinitrile functionalities into the scaffold of GA led to the discovery of potent compound 19 for inhibition of LPS-induced NO production. Furthermore, 19 effectively inhibited the protein and mRNA expression of inducible NO synthase (iNOS) and the mRNA expression of TNF-alpha, IL-6, and IL-1 beta in LPS-stimulated RAW 264.7 macrophages. Mechanistically, 19 exerted inhibitory effects on the activation of the three main MAPKs and phosphorylation and degradation of I kappa B-alpha, as well as the ratio of nuclear/cytosolic content of p65. Importantly, 19 significantly decreased the mortality rate in the mouse model of LPS-induced sepsis shock. It is noteworthy that inhibitory effect of 19 on NO production was not blocked by the glucocorticoid receptor antagonist mifepristone, indicating that it does not act through the glucocorticoid receptor.