3α,7β-dihydroxy-24-nor-5β-cholan-23-ol | 141417-52-9

• 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: 3α,7β-dihydroxy-24-nor-5β-cholan-23-ol
• 英文别名: 24-nor-5β-cholane-3α,7β,23-triol；24-Nor-5beta-cholane-3alpha,7beta,23-triol；(3R,5S,7S,8R,9S,10S,13R,14S,17R)-17-[(2R)-4-hydroxybutan-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: 141417-52-9
• 化学式: C₂₃H₄₀O₃
• 分子量: 364.569
• InChiKey: AQLBTYPFUGRFQI-KHLWDBHXSA-N

物化性质

• 沸点：
  497.8±20.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  3
• 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：

  3α,7β-dihydroxy-24-nor-5β-cholan-23-ol 在 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 生成 23-iodo-24-nor-5β-cholane-3α,7β-diol
  参考文献：
  名称：

  Synthesis of sulfonate analogs of bile acids

  摘要：

  Sulfonate analogs of C23 and C24 bile acids were synthesized from norcholic, norchenodeoxycholic, norursodeoxycholic, nordeoxycholic, norhyodeoxycholic, cholic, deoxycholic, hyodeoxycholic, and lithocholic acids. The principal reactions used were (1) reduction of the bile acids with NaBH4 to the corresponding bile alcohols, (2) selective tosylation of the terminal hydroxyl group, (3) iodination of the tosyl esters with NaI, and (4) treatment of the iodides with Na2SO3 to form the sulfonate analogs of the bile acids. The sulfonate analogs showed polarity similar to that of taurine-conjugated bile acids on thin-layer chromatography. The carbon 13 nuclear magnetic resonance spectral data for the sulfonate analogs were tabulated.

  DOI：

  10.1016/0039-128x(92)90008-w
• 作为产物：
  描述：

  24-去甲熊脱氧胆酸 在 sodium tetrahydroborate 、 氯甲酸乙酯 、 三乙胺 作用下， 生成 3α,7β-dihydroxy-24-nor-5β-cholan-23-ol
  参考文献：
  名称：

  Synthesis of sulfonate analogs of bile acids

  摘要：

  Sulfonate analogs of C23 and C24 bile acids were synthesized from norcholic, norchenodeoxycholic, norursodeoxycholic, nordeoxycholic, norhyodeoxycholic, cholic, deoxycholic, hyodeoxycholic, and lithocholic acids. The principal reactions used were (1) reduction of the bile acids with NaBH4 to the corresponding bile alcohols, (2) selective tosylation of the terminal hydroxyl group, (3) iodination of the tosyl esters with NaI, and (4) treatment of the iodides with Na2SO3 to form the sulfonate analogs of the bile acids. The sulfonate analogs showed polarity similar to that of taurine-conjugated bile acids on thin-layer chromatography. The carbon 13 nuclear magnetic resonance spectral data for the sulfonate analogs were tabulated.

  DOI：

  10.1016/0039-128x(92)90008-w

文献信息

• CHOLANE DERIVATIVES FOR USE IN THE TREATMENT AND/OR PREVENTION OF FXR AND TGR5/GPBAR1 MEDIATED DISEASES
  申请人：BAR PHARMACEUTICALS S.R.L.

  公开号：US20170190731A1

  公开（公告）日：2017-07-06

  The present invention relates to compounds having cholane scaffolds of formula (I), said compounds for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases.

  本发明涉及具有胆固醇骨架的化合物（I）的公式，所述化合物用于治疗和/或预防FXR和TGR5 / GPBAR1介导的疾病。
• Cholane derivatives for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases
  申请人：BAR PHARMACEUTICALS S.R.L.

  公开号：US10407462B2

  公开（公告）日：2019-09-10

  The present invention relates to compounds having cholane scaffolds of formula (I), said compounds for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases.

  本发明涉及具有式（I）胆烷支架的化合物，所述化合物用于治疗和/或预防 FXR 和 TGR5/GPBAR1 介导的疾病。
• Modification on Ursodeoxycholic Acid (UDCA) Scaffold. Discovery of Bile Acid Derivatives As Selective Agonists of Cell-Surface G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1)
  作者：Valentina Sepe、Barbara Renga、Carmen Festa、Claudio D’Amore、Dario Masullo、Sabrina Cipriani、Francesco Saverio Di Leva、Maria Chiara Monti、Ettore Novellino、Vittorio Limongelli、Angela Zampella、Stefano Fiorucci

  DOI：10.1021/jm500889f

  日期：2014.9.25

  Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3 alpha,7 beta-dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of proglucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.