(18β,20β)-3-(hydroxyimino)-11-oxo-olean-12-en-29-oic acid | 65941-05-1

• 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: (18β,20β)-3-(hydroxyimino)-11-oxo-olean-12-en-29-oic acid
• CAS: 65941-05-1
• 化学式: C₃₀H₄₅NO₄
• 分子量: 483.692
• InChiKey: NJKJHCFIFADRMH-LPXJIFNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.88
• 重原子数：
  35.0
• 可旋转键数：
  1.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  86.96
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (18β,20β)-3-(hydroxyimino)-11-oxo-olean-12-en-29-oic acid 在 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以40%的产率得到3a-Aza-3,11-dioxo-A-homo-olean-12-en-30-saeure
  参考文献：
  名称：

  Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors

  摘要：

  Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and type 2. Whereas inhibition of 11 beta-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11 beta-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11 beta-HSD2. The most potent and selective compound is active against human 11 beta-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11 beta-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11 beta-HSD1 and 11 beta-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11 beta-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.005
• 作为产物：
  描述：

  甘草次酸 在 吡啶 、 Jones reagent 、 盐酸羟胺 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 (18β,20β)-3-(hydroxyimino)-11-oxo-olean-12-en-29-oic acid
  参考文献：
  名称：

  Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors

  摘要：

  Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and type 2. Whereas inhibition of 11 beta-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11 beta-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11 beta-HSD2. The most potent and selective compound is active against human 11 beta-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11 beta-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11 beta-HSD1 and 11 beta-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11 beta-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.005

文献信息

• Improving the Thrombin Inhibitory Activity of Glycyrrhizin, a Triterpenic Saponin, Through a Molecular Simplification of the Carbohydrate Moiety
  作者：Fernando T. de Paula、Petrina Q. Frauches、Conrado Pedebos、Markus Berger、Simone C. B. Gnoatto、Grace Gossmann、Hugo Verli、Jorge A. Guimarães、Cedric S. Graebin

  DOI：10.1111/cbdd.12204

  日期：2013.12

  Glycyrrhizin, a saponin, and its aglycone glycyrrhetinic acid are natural products found in the Liquorice (Glycyrrhiza glabra L.) root extract. This saponin is known for its in vitro and in vivo thrombin inhibitory activity. The design and synthesis of five glycyrrhizin derivatives were carried out to improve the natural product activity. Compound 3b, a phthalic ester derivative of glycyrrhizin, presented a more pronounced thrombin inhibition (IC50 = 114.4 ± 1.3 μm) than the saponin (IC50 = 235.7 ± 1.4 μm). Molecular docking simulations performed to investigate the molecular interaction between compound 3b and the enzyme indicate that this product is, as previously determined for glycyrrhizin, an allosteric thrombin inhibitor.