Methyl-23nor-5β-cholonat | 6035-23-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: Methyl-23nor-5β-cholonat
• 英文别名: 24-nor-5β-cholanoic acid-(23)-methyl ester；24-Nor-5β-cholansaeure-(23)-methylester；Norcholanic acid methyl ester；methyl (3R)-3-[(5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butanoate
• CAS: 6035-23-0
• 化学式: C₂₄H₄₀O₂
• 分子量: 360.58
• InChiKey: JCEJAUVYYGKDSZ-LVVAJZGHSA-N

物化性质

• 沸点：
  395.5±10.0 °C(Predicted)
• 密度：
  0.994±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Methyl-23nor-5β-cholonat 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以100%的产率得到24-去甲-5beta-胆烷-23-酸
  参考文献：
  名称：

  Investigation on bile acid receptor regulators. Discovery of cholanoic acid derivatives with dual G-protein coupled bile acid receptor 1 (GPBAR1) antagonistic and farnesoid X receptor (FXR) modulatory activity

  摘要：

  Bile acids, the end products of cholesterol metabolism, activate multiple mechanisms through the interaction with membrane G-protein coupled receptors including the bile acid receptor GPBAR1 and nuclear receptors such as the bile acid sensor, farnesoid X receptor (FXR). Even if dual FXR/GPBAR1 agonists are largely considered a novel opportunity in the treatment of several liver and metabolic diseases, selective targeting of one of these receptors represents an attractive therapeutic approach for a wide range of disorders in which dual modulation is associated to severe side effects. In the present study we have investigated around the structure of LCA generating a small library of cholane derivatives, endowed with dual FXR agonism/GPBAR1 antagonism. To the best of our knowledge, this is the first report of bile acid derivatives able to antagonize GPBAR1. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2015.11.003
• 作为产物：
  描述：

  3α-formyloxy-5β-cholan-24-oic acid 在 吡啶 、 palladium hydroxide, 20 wt% on carbon 、 氢气 、 lithium carbonate 、 对甲苯磺酸 、 三氟乙酸 、 三氟乙酸酐 、 potassium hydroxide 、 lithium bromide 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 Methyl-23nor-5β-cholonat
  参考文献：
  名称：

  Investigation on bile acid receptor regulators. Discovery of cholanoic acid derivatives with dual G-protein coupled bile acid receptor 1 (GPBAR1) antagonistic and farnesoid X receptor (FXR) modulatory activity

  摘要：

  Bile acids, the end products of cholesterol metabolism, activate multiple mechanisms through the interaction with membrane G-protein coupled receptors including the bile acid receptor GPBAR1 and nuclear receptors such as the bile acid sensor, farnesoid X receptor (FXR). Even if dual FXR/GPBAR1 agonists are largely considered a novel opportunity in the treatment of several liver and metabolic diseases, selective targeting of one of these receptors represents an attractive therapeutic approach for a wide range of disorders in which dual modulation is associated to severe side effects. In the present study we have investigated around the structure of LCA generating a small library of cholane derivatives, endowed with dual FXR agonism/GPBAR1 antagonism. To the best of our knowledge, this is the first report of bile acid derivatives able to antagonize GPBAR1. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2015.11.003

文献信息

• A convenient new procedure for the oxidative cleavage of the bile acid and lanosterol side chains
  作者：M. Fetizon、F.J. Kakis、V. Ignatiadou-Ragoussis

  DOI：10.1016/s0040-4020(01)97373-9

  日期：1974.1

  A new method for the degradation of the side chain of lanosterol and bile acids is described. The cleavage was brought about by the action of molecular oxygen on basic solutions of the phenyl ketones (1, 7, and 15). Thus, the side chains were reduced by two C atoms, leading to the 23,24-bisnor series in appreciable yields. A method for converting the bisnor compounds to 20-ketosteroids is also described

  描述了一种用于降解羊毛甾醇和胆汁酸侧链的新方法。裂解物通过分子氧对苯基酮（的碱性溶液的作用带来的1，7，和15）。因此，侧链被两个C原子还原，从而以可观的收率得到23,24-bisnor系列。还描述了将比斯诺化合物转化为20-酮类固醇的方法。获得的结果表明，降解产物的性质取决于α-氢的酸度，反应介质的碱性强度和溶剂的性质。包括对该机制的简短讨论。
• Wieland; Schlichting; Jacobi, Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1926, vol. 161, p. 80,102
  作者：Wieland、Schlichting、Jacobi

  DOI：——

  日期：——
• Investigation on bile acid receptor regulators. Discovery of cholanoic acid derivatives with dual G-protein coupled bile acid receptor 1 (GPBAR1) antagonistic and farnesoid X receptor (FXR) modulatory activity
  作者：Valentina Sepe、Barbara Renga、Carmen Festa、Claudia Finamore、Dario Masullo、Adriana Carino、Sabrina Cipriani、Eleonora Distrutti、Stefano Fiorucci、Angela Zampella

  DOI：10.1016/j.steroids.2015.11.003

  日期：2016.1

  Bile acids, the end products of cholesterol metabolism, activate multiple mechanisms through the interaction with membrane G-protein coupled receptors including the bile acid receptor GPBAR1 and nuclear receptors such as the bile acid sensor, farnesoid X receptor (FXR). Even if dual FXR/GPBAR1 agonists are largely considered a novel opportunity in the treatment of several liver and metabolic diseases, selective targeting of one of these receptors represents an attractive therapeutic approach for a wide range of disorders in which dual modulation is associated to severe side effects. In the present study we have investigated around the structure of LCA generating a small library of cholane derivatives, endowed with dual FXR agonism/GPBAR1 antagonism. To the best of our knowledge, this is the first report of bile acid derivatives able to antagonize GPBAR1. (C) 2015 Elsevier Inc. All rights reserved.