奥贝胆酸杂质18 | 1537866-49-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: 奥贝胆酸杂质18
• 中文别名: 奥贝胆酸杂质
• 英文名称: 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-ol
• 英文别名: (3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-17-((R)-5-hydroxypentan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol；3α, 7α-dihydroxy-6α-ethyl-5β-cholan-24-ol；6alpha-Ethyl-5beta-cholane-3alpha,7alpha,24-triol；(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-17-[(2R)-5-hydroxypentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
• CAS: 1537866-49-1
• 化学式: C₂₆H₄₆O₃
• 分子量: 406.649
• InChiKey: DQBAHTQWQZRMFH-JDCMAIOWSA-N

物化性质

• 沸点：
  527.6±25.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  奥贝胆酸杂质18 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.5h， 生成 (5R)-5-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]hexanenitrile
  参考文献：
  名称：

  TETRAZOLE DERIVATIVES OF BILE ACIDS AS FXR/TGR5 AGONISTS AND METHODS OF USE THEREOF

  摘要：

  本发明提供了公式I的化合物：包括这些化合物的药物组合物和使用这些化合物治疗或预防由FXR和/或TGR5介导的疾病或疾病的方法。

  公开号：

  US20160145295A1
• 作为产物：
  描述：

  奥贝胆酸杂质48 在 甲醇 、 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 生成 奥贝胆酸杂质18
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Potent Dual Agonists of Nuclear and Membrane Bile Acid Receptors

  摘要：

  Bile acids exert genomic and nongenomic effects by interacting with membrane G-protein-coupled receptors, including the bile acid receptor GP-BAR1, and nuclear receptors, such as the farnesoid X receptor (FXR). These receptors regulate overlapping metabolic functions; thus, GP-BAR1/FXR dual agonists, by enhancing the biological response, represent an innovative strategy for the treatment of enteroendocrine disorders. Here, we report the design, total synthesis, and in vitro/in vivo pharmacological evaluation of a new generation of dual bile acid receptor agonists, with the most potent compound, 19, showing promising pharmacological profiles. We show that compound 19 activates GP-BAR1, FXR, and FXR regulated genes in the liver, increases the intracellular concentration of cAMP, and stimulates the release of the potent insulinotropic hormone GLP-1, resulting in a promising drug candidate for the treatment of metabolic disorders. We also elucidate the binding mode of the most potent dual agonists in the two receptors through a series of computations providing the molecular basis for dual GP-BAR1/FXR agonism.

  DOI：

  10.1021/jm401873d

文献信息

• Synthesis and characterization of new impurities in obeticholic acid
  作者：Wei-Dong Feng、Song-Ming Zhuo、Fu-Li Zhang

  DOI：10.1177/1747519819875858

  日期：2019.11

  Novel and efficient synthetic strategies are developed for the first synthesis of two new impurities found in obeticholic acid. The synthetic routes to the impurities are designed without column purification using 4-nitrobenzoyl chloride as a selective protecting group. The impurities, which are obtained in good yields and high purity, are identified and characterized using high-resolution mass spectrometry

  为首次合成在奥贝胆酸中发现的两种新杂质开发了新的高效合成策略。杂质的合成路线是使用 4-硝基苯甲酰氯作为选择性保护基团设计的，无需柱纯化。采用高分辨率质谱、傅里叶变换红外、一维核磁共振（1H、13C，极化转移无失真增强）和二维对以高收率和高纯度获得的杂质进行鉴定和表征。核磁共振（相关光谱、异核单量子相干、异核多键相关和旋转框架 Overhauser 效应光谱）技术。