胆甾-3,5-二烯酸甲酯 | 1172-10-7

• 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
• 中文名称: 胆甾-3,5-二烯酸甲酯
• 英文名称: methyl cholan-3,5-dien-24-oate
• 英文别名: Chola-3,5-dienic Acid Methyl Ester；methyl (4R)-4-[(8S,9S,10R,13R,14S,17R)-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 1172-10-7
• 化学式: C₂₅H₃₈O₂
• 分子量: 370.576
• InChiKey: QWJPYKBTCCHREN-XCLAERPWSA-N

物化性质

• 熔点：
  94-95 °C(Solv: methanol (67-56-1))
• 沸点：
  460.6±14.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)
• 溶解度：
  溶于DCM、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  胆甾-3,5-二烯酸甲酯 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.0h， 以100%的产率得到methyl 5α-cholan-24-oate
  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：

  methyl 3α,6α-ditosyloxy-5β-cholan-24-oate 在 potassium acetate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以78%的产率得到胆甾-3,5-二烯酸甲酯
  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

• Farnesoid X-activated receptor agonists
  申请人：——

  公开号：US20040014734A1

  公开（公告）日：2004-01-22

  The invention relates to compounds of formula (I) 1 in which n, R 3 , R 4 , R 5 , R 6 , R 10 , R 13 , R 17 , X, Y, and Z are defined above. The invention also relates to pharmaceutical compositions each containing an effective amount of one or more compounds of formula (I) and a pharmaceutically acceptable carrier.

  该发明涉及式(I)中化合物，其中n、R3、R4、R5、R6、R10、R13、R17、X、Y和Z如上所定义。该发明还涉及含有式(I)中一种或多种化合物的有效量和一种药用可接受载体的药物组合物。
• 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.