(3β,5β)-(2-hydroxy-2-methylpropyl)-cholan-24-oic acid

• 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: (3β,5β)-(2-hydroxy-2-methylpropyl)-cholan-24-oic acid
• 英文别名: (4R)-4-[(3S,5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-(2-methyl-2-oxidanyl-propyl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid；(4R)-4-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-(2-hydroxy-2-methylpropyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• 化学式: C₂₈H₄₈O₃
• 分子量: 432.687
• InChiKey: YEJWIEPCSOSHIJ-WDGWKBJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3α-tetrahydropyranyloxy-chol-24-ol 在 吡啶 、 甲醇 、 sodium tetrahydroborate 、 Jones reagent 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 sodium hydride 、 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 64.85h， 生成 (3β,5β)-(2-hydroxy-2-methylpropyl)-cholan-24-oic acid
  参考文献：
  名称：

  胆酸衍生物作为有效的维生素D受体激动剂

  摘要：

  Lithocholic acid (2) was identified as a second endogenous ligand of vitamin D receptor (VDR), though its activity is very weak. In this study, we designed novel lithocholic acid derivatives based on the crystal structure of VDR–ligand-binding domain (LBD) bound to 2. Among the synthesized compounds, 6 bearing a 2-hydroxy-2-methylprop-1-yl group instead of the 3-hydroxy group at the 3α-position of

  DOI：

  10.1021/acs.jmedchem.0c01420

文献信息

• Lithocholic acid-based design of noncalcemic vitamin D receptor agonists
  作者：Sunil Gaikwad、Carmen M. González、Daniel Vilariño、Gonzalo Lasanta、Carmen Villaverde、Antonio Mouriño、Lieve Verlinden、Annemieke Verstuyf、Carole Peluso-Iltis、Natacha Rochel、Klaudia Berkowska、Ewa Marcinkowska

  DOI：10.1016/j.bioorg.2021.104878

  日期：2021.6

  hormone 1α,25-dihydroxyvitamin D3 (calcitriol) and most of known vitamin D metabolites and analogs call for the development of non secosteroidal vitamin D receptor (VDR) ligands as new selective and noncalcemic agonists for treatment of hyperproliferative diseases. We report on the in silico design and stereoselective synthesis of six lithocholic acid derivatives as well as on the calcemic activity

  激素 1α,25-二羟基维生素 D 3（骨化三醇）和大多数已知维生素 D 代谢物和类似物的高钙血症作用需要开发非甾体维生素 D 受体 (VDR) 配体作为治疗过度增殖性疾病的新型选择性和非钙血症激动剂. 我们报告了六种石胆酸衍生物的计算机设计和立体选择性合成，以及一种有效的 LCA 衍生物的钙血活性及其与 zVDR LBD 复合物的晶体结构。与天然激素相比，该化合物的低钙血活性使其具有潜在的治疗价值。结构-功能关系为开发更有效和更具选择性的基于石胆酸的 VDR 配体提供了基础。
• Lithocholic Acid Derivatives as Potent Vitamin D Receptor Agonists
  作者：Harue Sasaki、Hiroyuki Masuno、Haru Kawasaki、Ayana Yoshihara、Nobutaka Numoto、Nobutoshi Ito、Hiroaki Ishida、Keiko Yamamoto、Naoya Hirata、Yasunari Kanda、Emiko Kawachi、Hiroyuki Kagechika、Aya Tanatani

  DOI：10.1021/acs.jmedchem.0c01420

  日期：2021.1.14

  Lithocholic acid (2) was identified as a second endogenous ligand of vitamin D receptor (VDR), though its activity is very weak. In this study, we designed novel lithocholic acid derivatives based on the crystal structure of VDR–ligand-binding domain (LBD) bound to 2. Among the synthesized compounds, 6 bearing a 2-hydroxy-2-methylprop-1-yl group instead of the 3-hydroxy group at the 3α-position of

  Lithocholic acid (2) was identified as a second endogenous ligand of vitamin D receptor (VDR), though its activity is very weak. In this study, we designed novel lithocholic acid derivatives based on the crystal structure of VDR–ligand-binding domain (LBD) bound to 2. Among the synthesized compounds, 6 bearing a 2-hydroxy-2-methylprop-1-yl group instead of the 3-hydroxy group at the 3α-position of