methyl 7α-hydroxy-5β-cholan-24-oate | 28050-19-3

• 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 7α-hydroxy-5β-cholan-24-oate
• 英文别名: Methyl 7α-hydroxy-5β-cholanate；Methyl 7α-hydroxycholanate；7α-hydroxy-5β-cholan-24-oic acid methyl ester；7α-Hydroxy-5β-cholan-24-saeure-methylester；7alpha-Hydroxy-5beta-cholan-24-oic acid Methyl ester；methyl (4R)-4-[(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 28050-19-3
• 化学式: C₂₅H₄₂O₃
• 分子量: 390.607
• InChiKey: SLMFZEZJHJUPDN-IGANSQQNSA-N

物化性质

• 沸点：
  474.2±18.0 °C(Predicted)
• 密度：
  1.038±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 7α-hydroxy-5β-cholan-24-oate 在 sodium tetrahydroborate 、 potassium chromate 作用下， 生成 (5beta,7alpha)-7-羟基胆烷-24-酸
  参考文献：
  名称：

  Preparation and NaBH₄ Reduction of 7-Ketocholanic Acid

  摘要：

  DOI：

  10.1021/ja01651a064
• 作为产物：
  描述：

  methyl 7-keto-5β-cholan-24-oate 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以100%的产率得到methyl 7α-hydroxy-5β-cholan-24-oate
  参考文献：
  名称：

  Exploitation of Cholane Scaffold for the Discovery of Potent and Selective Farnesoid X Receptor (FXR) and G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1) Ligands

  摘要：

  Nuclear and G-protein coupled receptors are considered major targets for drug discovery. FXR and GP-BAR1, two bile acid-activated receptors, have gained increasing consideration as druggable receptors. Because endogenous bile acids often target both receptor families, the development of selective ligands has been proven difficult, exposing patients to side effects linked to an unwanted activation of one of the two receptors. In the present study, we describe a novel library of semisynthetic bile acid derivatives obtained by modifications on the cholane scaffold. The pharmacological characterization of this library led to the discovery of 7a-hydroxy-5 beta-cholan-24-sulfate (7), 6 beta-ethyl-3a,7 beta-dihydroxy-5 beta-cholan-24-ol (EUDCOH, 26), and 6a-ethyl-3a, 7a-dihydroxy-24-nor-5 beta-cholan-23-ol (NorECDCOH, 30) as novel ligands for FXR and GP-BAR1 that might hold utility in the treatment of FXR and GP-BAR1 mediated disorders.

  DOI：

  10.1021/jm501273r

文献信息

• Improved Conditions for Preparation and Reductive Cleavage of Steroidal Ketone Tosylhydrazones
  作者：Takashi Iida、Toshitake Tamura、Taro Matsumoto、Frederic C. Chang

  DOI：10.1055/s-1984-31036

  日期：——
• Preparation and NaBH₄ Reduction of 7-Ketocholanic Acid
  作者：E. H. Mosbach、W. Meyer、F. E. Kendall

  DOI：10.1021/ja01651a064

  日期：1954.11
• Potential bile acid metabolites. 8. 7,12-Dihydroxy- and 7.beta.-hydroxy-5.beta.-cholanic acids
  作者：Takashi Iida、Frederic C. Chang

  DOI：10.1021/jo00156a010

  日期：1983.4
• Exploitation of Cholane Scaffold for the Discovery of Potent and Selective Farnesoid X Receptor (FXR) and G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1) Ligands
  作者：Carmen Festa、Barbara Renga、Claudio D’Amore、Valentina Sepe、Claudia Finamore、Simona De Marino、Adriana Carino、Sabrina Cipriani、Maria Chiara Monti、Angela Zampella、Stefano Fiorucci

  DOI：10.1021/jm501273r

  日期：2014.10.23

  Nuclear and G-protein coupled receptors are considered major targets for drug discovery. FXR and GP-BAR1, two bile acid-activated receptors, have gained increasing consideration as druggable receptors. Because endogenous bile acids often target both receptor families, the development of selective ligands has been proven difficult, exposing patients to side effects linked to an unwanted activation of one of the two receptors. In the present study, we describe a novel library of semisynthetic bile acid derivatives obtained by modifications on the cholane scaffold. The pharmacological characterization of this library led to the discovery of 7a-hydroxy-5 beta-cholan-24-sulfate (7), 6 beta-ethyl-3a,7 beta-dihydroxy-5 beta-cholan-24-ol (EUDCOH, 26), and 6a-ethyl-3a, 7a-dihydroxy-24-nor-5 beta-cholan-23-ol (NorECDCOH, 30) as novel ligands for FXR and GP-BAR1 that might hold utility in the treatment of FXR and GP-BAR1 mediated disorders.