7α-hydroxy-5β-cholan-24-oyl taurine sodium

• 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: 7α-hydroxy-5β-cholan-24-oyl taurine sodium
• 英文别名: sodium;2-[[(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]pentanoyl]amino]ethanesulfonate
• 化学式: C₂₆H₄₄NO₅S*Na
• 分子量: 505.695
• InChiKey: KLGGTQLXIQHTMW-FXRALWMISA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.09
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 7-keto-5β-cholan-24-oate 在 sodium tetrahydroborate 、 三乙胺 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.17h， 生成 7α-hydroxy-5β-cholan-24-oyl taurine sodium
  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

• 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.