methyl 3α-tosyloxy-7α-hydroxy-5β-cholan-24-oate | 28192-93-0

• 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 3α-tosyloxy-7α-hydroxy-5β-cholan-24-oate
• 英文别名: methyl 3α-p-toluenesulfonyl-7α-hydroxy-5β-cholest-24-carboxylate；O-Tosyl Chenodeoxycholic Acid Methyl Ester；methyl (4R)-4-[(3R,5R,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-(4-methylphenyl)sulfonyloxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 28192-93-0
• 化学式: C₃₂H₄₈O₆S
• 分子量: 560.796
• InChiKey: FZCZUIIHRDQSLU-SONPXKAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.29
• 重原子数：
  39.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  89.9
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 3α-tosyloxy-7α-hydroxy-5β-cholan-24-oate 在 吡啶 、 2,6-二甲基吡啶 、 氢氧化钾 、 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 甲醇 、 水 、 叔丁醇 为溶剂， 反应 4.0h， 生成 3β,4β,7α-trihydroxy-5β-cholanoic acid
  参考文献：
  名称：

  潜在的胆汁酸代谢物。十五 4β-羟基化胆汁酸的合成；人胎儿胆汁中独特的胆汁酸。

  摘要：

  由它们各自的母体化合物合成了石胆酸，脱氧胆酸，鹅去氧胆酸和胆酸的4个β-羟基化衍生物。所采用的主要反应是1）用四氧化-N-甲基吗啉N-氧化物对delta 3中间体进行β-面顺-二羟基化； 2）对邻位3 beta，4β-二醇进行选择性催化氧化，然后将所得4β-单羧酸盐，或用氯铬酸吡啶鎓在C-3处直接选择性氧化3个beta，4个β-二醇，以及3）用叔丁胺-硼烷络合物立体选择性还原3-氧代化合物。

  DOI：

  10.1248/cpb.37.3323
• 作为产物：
  描述：

  3alpha,7alpha-二乙酰氧基-12-氧代-5beta-胆烷-24-酸甲酯 在 吡啶 、 盐酸 、 hydrazine hydrate 、 potassium hydroxide 作用下， 以 水 、 乙二醇 为溶剂， 反应 12.0h， 生成 methyl 3α-tosyloxy-7α-hydroxy-5β-cholan-24-oate
  参考文献：
  名称：

  一类鹅去氧胆酸衍生物、其制备方法和医药用 途

  摘要：

  本发明涉及药物化学领域，涉及鹅去氧胆酸衍生物、其制备方法和医药用途，具体涉及一类通式为(I)的鹅去氧胆酸衍生物、它们的制备方法、含有这些化合物的药物组合物以及它们的医药用途，特别是作为预防或治疗高脂血症、II型糖尿病、动脉粥样硬化、非酒精性脂肪肝炎的药物的用途。

  公开号：

  CN107987116B

文献信息

• Potential bile acid metabolites. 6. Stereoisomeric 3,7-dihydroxy-5.beta.-cholanic acids
  作者：Takashi Iida、Frederic C. Chang

  DOI：10.1021/jo00136a030

  日期：1982.7
• Lipid accumulation inhibitory activities of novel isoxazole-based chenodeoxycholic acids: Design, synthesis and preliminary mechanism study
  作者：Rongmao Qiu、Guoshun Luo、Xinyu Li、Fan Zheng、Haolin Li、Jin Zhang、Qidong You、Hua Xiang

  DOI：10.1016/j.bmcl.2018.07.026

  日期：2018.9

  In continuation of our drug discovery program on hyperlipidemia, a series of novel isoxazole-chenodeoxycholic acid hybrids were designed, synthesized and evaluated for their lipid-lowering effects. Preliminary screening of all the synthesized compounds was done by using a 3T3-L1 adipocyte model, in which the most active compound 16b could significantly reduce the lipid accumulation up to 30.5% at a nontoxic concentration 10 mu M. Further mechanism studies revealed that 16b blocked lipid accumulation via activating FXR-SHP signaling pathway, efficiently down-regulated the expression of key lipogenesis regulator SREBP-1c.
• Sawaya, Takuji; Kimura, Michiya, Chemical and pharmaceutical bulletin, 1983, vol. 31, # 4, p. 1207 - 1212
  作者：Sawaya, Takuji、Kimura, Michiya

  DOI：——

  日期：——
• 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.
• Methyl 3β-Bromine-7α-hydroxy-5β-cholan-24-oate
  作者：A. D. Morales、R. Pomés Hernández、F. C. Manchado、R. P. Gil、G. Punte、G. Echeverría

  DOI：10.1107/s0108270197007464

  日期：1997.12.15

  In the title compound, C25H41BrO3, the Br atom bonded to C3 is beta-axially oriented and is (-)-synclinal to the C4-C5 bond. The six-membered rings (A, B and C) have chair conformations as expected. The five membered ring (D) adopts a distorted 13 beta-envelope conformation. The A/B ring junction is cis and the B/C and C/D ring junctions are both trans.