(3α,18β,20β)-3-methoxyamino-11-oxo-olean-12-en-29-oic acid | 1257902-36-5

• 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: (3α,18β,20β)-3-methoxyamino-11-oxo-olean-12-en-29-oic acid
• 英文别名: (3alpha,18beta,20beta)-3-Methoxyamino-11-oxo-olean-12-en-29-oic acid hydrochloride；(2S,4aS,6aR,6aS,6bR,8aR,10R,12aS,14bR)-10-(methoxyamino)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid
• CAS: 1257902-36-5
• 化学式: C₃₁H₄₉NO₄
• 分子量: 499.734
• InChiKey: DEBAOVSKKCPBDP-RQJBKSHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3α,18β,20β)-3-methoxyamino-11-oxo-olean-12-en-29-oic acid diphenylmethyl ester 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 (3α,18β,20β)-3-methoxyamino-11-oxo-olean-12-en-29-oic acid
  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.