benzyl 3α-benzyloxycarboxy-7α,12α-dihydroxy-5β-cholan-24-oate | 1323923-68-7

• 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: benzyl 3α-benzyloxycarboxy-7α,12α-dihydroxy-5β-cholan-24-oate
• 英文别名: benzyl 3α-benzyloxycarboxy-7α,12α-dihydroxy-5β-cholate
• CAS: 1323923-68-7
• 化学式: C₃₉H₅₂O₇
• 分子量: 632.838
• InChiKey: ZYNDCPBTXSKMDI-QDFLWEJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.47
• 重原子数：
  46.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  102.29
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  benzyl 3α-benzyloxycarboxy-7α,12α-dihydroxy-5β-cholan-24-oate 在 calcium hydride 、 palladium 10% on activated carbon 、 ammonium acetate 、 苄基三乙基溴化铵 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 3.0h， 生成 7α,12α-bis(decanoyloxy)-3α-hydroxy-5β-cholic acid
  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：

  氯甲酸苄酯 、 benzyl cholate 在 吡啶 作用下， 反应 24.0h， 以46%的产率得到benzyl 3α-benzyloxycarboxy-7α,12α-dihydroxy-5β-cholan-24-oate
  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

文献信息

• New polyfluorothiopropanoyloxy derivatives of 5β-cholan-24-oic acid designed as drug absorption modifiers
  作者：Lech Mrózek、Lenka Coufalová、Lucie Rárová、Lukáš Plaček、Radka Opatřilová、Jiří Dohnal、Katarína Kráľová、Oldřich Paleta、Vladimír Král、Pavel Drašar、Josef Jampílek

  DOI：10.1016/j.steroids.2013.05.012

  日期：2013.9

  A series of final six propanoyloxy derivatives of 5 beta-cholan-24-oic acid (tridecafluoroctylsulfanyl- and tridecafluoroctylsulfinylethoxycarbonylpropanoyloxy derivatives) as potential drug absorption promoters (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 leukaemia cell line and breast adenocarcinoma cell line. One compound showed high selective cytotoxicity against human skin fibroblast cells and another compound possessed high cytotoxicity against breast adenocarcinoma cell line and skin fibroblast cells. Only one compound expressed anti-proliferative effect on leukaemia and breast adenocarcinoma 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 penetration enhancement effect are discussed in this article. (C) 2013 Elsevier Inc. All rights reserved.