7α,12α-bis{3-[2-(2-decanoyloxyethoxy)ethoxycarbonyl]propanoyloxy}-3α-hydroxy-5β-cholan-24-oic acid | 1430196-61-4

• 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: 7α,12α-bis{3-[2-(2-decanoyloxyethoxy)ethoxycarbonyl]propanoyloxy}-3α-hydroxy-5β-cholan-24-oic acid
• 英文别名: (4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-7,12-bis[[4-[2-(2-decanoyloxyethoxy)ethoxy]-4-oxobutanoyl]oxy]-3-hydroxy-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
• CAS: 1430196-61-4
• 化学式: C₆₀H₁₀₀O₁₇
• 分子量: 1093.44
• InChiKey: KNRCNOJEIHHDGV-IEIPGTSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.9
• 重原子数：
  77
• 可旋转键数：
  46
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  234
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  benzyl 3α-benzyloxycarboxy-7α,12α-bis{3-[2-(2-decanoyloxyethoxy)ethoxycarbonyl]propanoyloxy}-5β-cholan-24-oate 在 palladium 10% on activated carbon 、 ammonium formate 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 1.5h， 以74%的产率得到7α,12α-bis{3-[2-(2-decanoyloxyethoxy)ethoxycarbonyl]propanoyloxy}-3α-hydroxy-5β-cholan-24-oic acid
  参考文献：
  名称：

  New propanoyloxy derivatives of 5β-cholan-24-oic acid as drug absorption modifiers

  摘要：

  A series of final twelve propanoyloxy derivatives of 5 beta-cholan-24-oic acid (O-propanoyl derivatives of cholic acid) as potential drug absorption modifiers (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by H-1 NMR, C-13 NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R-M) was determined. The hydrophobicity (log P), solubility (log S), polar surface area (PSA) and molar volume (MV) of the studied compounds were also calculated. All the target compounds were tested for their in vitro transdermal. penetration effect and as potential intestinal absorption enhancers. The cytotoxicity of all the evaluated compounds was evaluated against normal human skin fibroblast cells. Their anti-proliferative activity was also assessed against human cancer cell lines: T-lymphoblastic leukemia cell line and breast adenocarcinoma cell line. One compound showed selective cytotoxicity against human skin fibroblast cells and another compound possessed the highest cytotoxicity against all the tested cell lines. Only one compound expressed anti-proliferative effect on leukemia cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC50 > 37 mu M), indicating they would have moderate cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity/polarity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effect are discussed in this article. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2013.02.001