(2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-((3-methoxy-3-oxopropyl)sulfonamido)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic acid | 1257867-13-2

• 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: (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-((3-methoxy-3-oxopropyl)sulfonamido)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic acid
• 英文别名: (3β,18β,20β)-3-(2-methoxycarbonyl-ethylsulfonylamino)-11-oxo-olean-12-en-29-oic acid；(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-[(3-methoxy-3-oxopropyl)sulfonylamino]-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: 1257867-13-2
• 化学式: C₃₄H₅₃NO₇S
• 分子量: 619.863
• InChiKey: KPQYDJPPEPBZOI-AWTOMRQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-((3-methoxy-3-oxopropyl)sulfonamido)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic acid 在 水 、 sodium hydroxide 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以97%的产率得到(3β,18β,20β)-3-(2-carbonyl-ethylsulfonylamino)-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
• 作为产物：
  描述：

  benzhydryl (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-((3-methoxy-3-oxopropyl)sulfonamido)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以97.8%的产率得到(2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-((3-methoxy-3-oxopropyl)sulfonamido)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic 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

• [EN] GLYCYRRHETINIC ACID DERIVATIVES FOR TREATING HYPERKALEMIA<br/>[FR] DÉRIVÉS D'ACIDE GLYCYRRHÉTINIQUE DE TRAITEMENT DE L'HYPERKALIÉMIE
  申请人：ARDELYX INC

  公开号：WO2019060051A1

  公开（公告）日：2019-03-28

  The present invention provides a compound of formula (I) or a salt thereof: (I) wherein X, L, V, R1, R2, R3 and R4, are as defined herein. These compounds are inhibitors of 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) and are used to treat hyperkalemia.

  本发明提供了化合物(I)或其盐：(I)其中X、L、V、R1、R2、R3和R4如本文所定义。这些化合物是11-羟基类固醇脱氢酶2型（11-HSD-2）的抑制剂，用于治疗高钾血症。
• GLYCYRRHETINIC ACID DERIVATIVES FOR TREATING HYPERKALEMIA
  申请人：Ardelyx, Inc.

  公开号：US20210163524A1

  公开（公告）日：2021-06-03

  The present invention provides a compound of formula (I) or a salt thereof: (I) wherein X, L, V, R 1 , R 2 , R 3 and R 4 , are as defined herein. These compounds are inhibitors of 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) and are used to treat hyperkalemia.
• 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.