(9β,13α,14β,20α)-2-methoxy-3-hydroxy-9,13-dimethyl-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (9β,13α,14β,20α)-2-methoxy-3-hydroxy-9,13-dimethyl-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
• 英文别名: (2R,4aS,6aS,6aS,14aS,14bR)-10-hydroxy-11-methoxy-2,4a,6a,6a,9,14a-hexamethyl-3,4,5,6,8,13,14,14b-octahydro-1H-picene-2-carboxylic acid
• 化学式: C₃₀H₄₂O₄
• 分子量: 466.661
• InChiKey: JMNRNEHNJHDDFP-WXPPGMDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  雷公藤红素 在 sodium tetrahydroborate 、 碳酸氢钠 、 potassium carbonate 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 氘代甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 28.5h， 生成 (9β,13α,14β,20α)-2-methoxy-3-hydroxy-9,13-dimethyl-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
  参考文献：
  名称：

  SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway

  摘要：

  Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent manner. Celastrol binding to Nur77 promotes Nur77 translocation from nucleus to cytoplasm, resulting in clearance of inflamed mitochondria and then alleviation of inflammation. Here, we report the design, synthesis, SAR study and biological evaluation of a series of celastrol analogs. A total of 24 celastrol derivatives were made. Compound 3a with a K-d of 0.87 mu M was found to be less toxic than celastrol and could be a hit molecule for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.009

文献信息

• SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway
  作者：Ziwen Chen、Duo Zhang、Siwei Yan、Chaochao Hu、Zhenfei Huang、Zhuoer Li、Shuangzhou Peng、Xiaotong Li、Yi Zhu、Hongyu Yu、Baohuan Lian、Qi Kang、Mingyu Li、Zhiping Zeng、Xiao-Kun Zhang、Ying Su

  DOI：10.1016/j.ejmech.2019.05.009

  日期：2019.9

  Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent manner. Celastrol binding to Nur77 promotes Nur77 translocation from nucleus to cytoplasm, resulting in clearance of inflamed mitochondria and then alleviation of inflammation. Here, we report the design, synthesis, SAR study and biological evaluation of a series of celastrol analogs. A total of 24 celastrol derivatives were made. Compound 3a with a K-d of 0.87 mu M was found to be less toxic than celastrol and could be a hit molecule for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.