(3-β,18β,20β)-N-hydroxy-N-methyl-3-methoxyamino-11-oxo-olean-12-en-29-amide | 1243659-90-6

• 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: (3-β,18β,20β)-N-hydroxy-N-methyl-3-methoxyamino-11-oxo-olean-12-en-29-amide
• 英文别名: (2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-N-hydroxy-10-(methoxyamino)-N,2,4a,6a,6b,9,9,12a-octamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxamide
• CAS: 1243659-90-6
• 化学式: C₃₂H₅₂N₂O₄
• 分子量: 528.776
• InChiKey: WFFRYDDMEOSCOR-XWEVEMRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (18β,20β)-N-hydroxy-N-methyl-3-methoxyimino-11-oxo-olean-12-en-29-amide 在 盐酸 、 C₄H₁₂BN*H⁽¹⁺⁾ 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 以18.1%的产率得到(3-β,18β,20β)-N-hydroxy-N-methyl-3-methoxyamino-11-oxo-olean-12-en-29-amide
  参考文献：
  名称：

  Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid 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. So far, no selective 11 beta-HSD2 inhibitor has been developed and neither animal studies nor clinical trials have been reported based on 11 beta-HSD2 inhibition. Starting from the lead compound glycyrrhetinic acid, 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. Several hydroxamic acid derivatives showed 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. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.046

文献信息

• Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors
  作者：Christian Stanetty、Laszlo Czollner、Iris Koller、Priti Shah、Rawindra Gaware、Thierry Da Cunha、Alex Odermatt、Ulrich Jordis、Paul Kosma、Dirk Claßen-Houben

  DOI：10.1016/j.bmc.2010.08.046

  日期：2010.11

  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. So far, no selective 11 beta-HSD2 inhibitor has been developed and neither animal studies nor clinical trials have been reported based on 11 beta-HSD2 inhibition. Starting from the lead compound glycyrrhetinic acid, 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. Several hydroxamic acid derivatives showed 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. (C) 2010 Elsevier Ltd. All rights reserved.