methyl (3β,5β,7α,12α)-7,12-dixydroxy-3-(2-hydroxyethoxy)cholan-24-oate | 135053-66-6

• 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 (3β,5β,7α,12α)-7,12-dixydroxy-3-(2-hydroxyethoxy)cholan-24-oate
• 英文别名: Methyl(3beta,5beta,7alpha,12alpha)-7,12-dihydroxy-3-(2-hydroxyethoxy)cholan-24-oate；methyl (4R)-4-[(3S,5R,7R,8R,9S,10S,12S,13R,14S,17R)-7,12-dihydroxy-3-(2-hydroxyethoxy)-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: 135053-66-6
• 化学式: C₂₇H₄₆O₆
• 分子量: 466.659
• InChiKey: ZKQIOSQOAJJHJF-RXUFXJRISA-N

物化性质

• 沸点：
  584.9±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (3β,5β,7α,12α)-7,12-dixydroxy-3-(2-hydroxyethoxy)cholan-24-oate 在 N-溴代丁二酰亚胺(NBS) 、 N,N-二异丙基乙胺 、 三苯基膦 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 19.0h， 生成 methyl (3β,5β,7α,12α)-7,12-dihydroxy-3-{2-[{4-[(11β,17α)-17-hydroxy-3-oxo-17-prop-1-ynylestra-4,9-dien-11-yl]phenyl}(methyl)amino]ethoxy}cholan-24-oate
  参考文献：
  名称：

  肝选择性糖皮质激素拮抗剂：一种用于2型糖尿病的新型治疗方法。

  摘要：

  肝脏对糖皮质激素受体（GR）的阻滞抑制了葡萄糖的产生，从而降低了循环葡萄糖的水平，但是全身性糖皮质激素拮抗作用会产生肾上腺功能不全和其他不良副作用。当GR拮抗剂以适当的方式与胆汁酸相连时，这些肝和全身反应可能会被分解，从而导致肝脏选择性药理学。胆汁酸结合可以在对GR的结合亲和力损失最小的情况下完成。所得的缀合物在基于细胞的功能测定中仍然有效。已经开发出一种新颖的体内测定法，以同时评估肝和全身性GR阻滞。该测定法已用于优化接头功能的性质和位点，以及选择GR拮抗剂和胆汁酸。

  DOI：

  10.1021/jm0400045
• 作为产物：
  描述：

  胆酸 在 吡啶 、 盐酸 作用下， 反应 14.5h， 生成 methyl (3β,5β,7α,12α)-7,12-dixydroxy-3-(2-hydroxyethoxy)cholan-24-oate
  参考文献：
  名称：

  Modified bile acids: preparation of 7α,12α-dihydroxy-3β- and 7α,12α-dihydroxy-3α-(2-hydroxyethoxy)-5β-cholanic acid and their biological activity

  摘要：

  Methodology for the preparation of 7-alpha,12-alpha-dihydroxy-3-beta- (2) and 7-alpha,12-alpha-dihydroxy-3-alpha-(2-hydroxyethoxy)-5-beta-cholanic acid (3) is described. Nucleophilic displacement of the 3-mesylate of unprotected cholic acid with ethylene glycol led to the 3-beta-isomer whereas the 3-alpha-isomer was synthesized via the 7,12-diacetyl protected 3-allyl ether of methyl cholate. Only the 3-alpha-isomer 3 is recognized by the ileal bile acid transport system with affinity comparable to cholic acid.

  DOI：

  10.1016/0040-4039(92)88048-a

文献信息

• [EN] GLUCOCORTICOID RECEPTOR LIGANDS FOR THE TREATMENT OF METABOLIC DISORDERS<br/>[FR] LIGANDS DE RECEPTEURS GLUCOCORTICOIDES POUR LE TRAITEMENT DE TROUBLES METABOLIQUES
  申请人：ABBOTT LAB

  公开号：WO2004000869A1

  公开（公告）日：2003-12-31

  This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.

  这项发明涉及一种新型化合物，它们是肝选择性糖皮质激素受体拮抗剂，涉及制备这种化合物的方法，以及利用这种化合物在调节新陈代谢方面的方法，特别是降低血清葡萄糖水平、胰岛素水平或脂质水平，和/或减少体重。
• Synthesis of 1,2,3-Triazole-containing Bile Acid Dimers and Properties of Inverse Micellar Mimic
  作者：Zhen Zhang、Yong Ju、Yufen Zhao

  DOI：10.1246/cl.2007.1450

  日期：2007.12.5

  Six new 1,2,3-triazole-containing bile acid dimers, involving head-to-tail, head-to-head, and tail-to-tail three types of steroidal derivatives, have been synthesized via Cu 1 -catalyzed 1,3-dipolar cycloaddition reaction "click chemistry" in high yields. The inverse micellar properties of these compounds were also investigated through hydrophilic dye solubilization studies in nonpolar media.

  通过Cu 1 催化合成了六个新的含1,2,3-三唑的胆汁酸二聚体，涉及头对尾、头对头和尾对尾三种甾体衍生物，高产率的 3-偶极环加成反应“点击化学”。这些化合物的反胶束特性也通过非极性介质中的亲水染料增溶研究进行了研究。
• Novel glucocorticoid receptor ligands for the treatment of metabolic disorders
  申请人：——

  公开号：US20040235810A1

  公开（公告）日：2004-11-25

  This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.

  本发明涉及一种肝脏选择性糖皮质激素受体拮抗剂的新化合物，涉及制备这种化合物的方法，以及利用这种化合物在调节新陈代谢方面的方法，特别是降低血清葡萄糖水平、胰岛素水平或脂质水平，和/或减轻体重。
• Glucocorticoid receptor ligands for the treatment of metabolic disorders
  申请人：Karo Bio AB

  公开号：US07141559B2

  公开（公告）日：2006-11-28

  This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.

  本发明涉及一种新型化合物，其为肝脏选择性糖皮质激素受体拮抗剂，涉及制备这种化合物的方法，以及使用这种化合物调节新陈代谢的方法，特别是降低血清葡萄糖水平、胰岛素水平或脂质水平，和/或减轻体重。
• Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator
  作者：Noah Tu、J.T Link、Bryan K Sorensen、Maurice Emery、Marlena Grynfarb、Annika Goos-Nilsson、Bach Nguyen

  DOI：10.1016/j.bmcl.2004.06.022

  日期：2004.8

  Bile acid conjugates of a selective nonsteroidal glucocorticoid receptor modulator were prepared and evaluated. Potent GR binding conjugates that showed improved metabolic stability were discovered. However, cellular potency and pharmacokinetics were not substantially improved. (C) 2004 Elsevier Ltd. All rights reserved.