(2S,4aS,6aR,6bS,8aR,12aR,14bR)-11-hydroxy-N,2,4a,6a,6b,9,9,12a-octamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxamide | 1402570-99-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2S,4aS,6aR,6bS,8aR,12aR,14bR)-11-hydroxy-N,2,4a,6a,6b,9,9,12a-octamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxamide
• CAS: 1402570-99-3
• 化学式: C₃₁H₄₅NO₃
• 分子量: 479.703
• InChiKey: WAQMCIHRHFFWPK-UNNRZNSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  35
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  甘草次酸 在 盐酸 、 sodium tetrahydroborate 、 草酰氯 、 potassium tert-butylate 、 sodium hydroxide 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 55.5h， 生成 (2S,4aS,6aR,6bS,8aR,12aR,14bR)-11-hydroxy-N,2,4a,6a,6b,9,9,12a-octamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxamide
  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

• 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.