tert-butyl 3α-decanoyloxy-7α-hydroxy-12α-trifluoroacetoxy-5β-cholate | 1323923-63-2

• 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: tert-butyl 3α-decanoyloxy-7α-hydroxy-12α-trifluoroacetoxy-5β-cholate
• CAS: 1323923-63-2
• 化学式: C₄₀H₆₅F₃O₇
• 分子量: 714.947
• InChiKey: QJPCUADYIBRKOT-XVKYSDNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.51
• 重原子数：
  50.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  99.13
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 3α-decanoyloxy-7α-hydroxy-12α-trifluoroacetoxy-5β-cholate 在 氨 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以90%的产率得到tert-butyl 3α-decanoyloxy-7α,12α-dihydroxy-5β-cholate
  参考文献：
  名称：

  Investigation of new acyloxy derivatives of cholic acid and their esters as drug absorption modifiers

  摘要：

  Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. Intestinal absorption promoters/enhancers are used as excipients in oral formulations of poorly oral-bioavailable drugs. Series of fourteen acyloxy derivatives of 5 beta-cholic acid as potential drug absorption modifiers was generated by multistep synthesis. The synthesis of all newly prepared compounds is presented here. 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) and solubility (logS) of the studied compounds were also calculated using two commercially available programs. All the target compounds were tested for their in vitro transdermal penetration activity and as potential intestinal absorption enhancers. The anti-proliferative activity of all the final compounds was also assessed against the human cancer cell lines: T-lymphoblastic leukemia cell line and the breast adenocarcinoma cell line. Their cytotoxicity was also evaluated against the normal human skin fibroblast cells. Two compounds showed anti-proliferative effect on 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 low cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effects are discussed in this article. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.04.014
• 作为产物：
  描述：

  胆酸 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.83h， 生成 tert-butyl 3α-decanoyloxy-7α-hydroxy-12α-trifluoroacetoxy-5β-cholate
  参考文献：
  名称：

  Investigation of new acyloxy derivatives of cholic acid and their esters as drug absorption modifiers

  摘要：

  Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. Intestinal absorption promoters/enhancers are used as excipients in oral formulations of poorly oral-bioavailable drugs. Series of fourteen acyloxy derivatives of 5 beta-cholic acid as potential drug absorption modifiers was generated by multistep synthesis. The synthesis of all newly prepared compounds is presented here. 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) and solubility (logS) of the studied compounds were also calculated using two commercially available programs. All the target compounds were tested for their in vitro transdermal penetration activity and as potential intestinal absorption enhancers. The anti-proliferative activity of all the final compounds was also assessed against the human cancer cell lines: T-lymphoblastic leukemia cell line and the breast adenocarcinoma cell line. Their cytotoxicity was also evaluated against the normal human skin fibroblast cells. Two compounds showed anti-proliferative effect on 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 low cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effects are discussed in this article. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.04.014