benzyl 3α-butanoyloxy-7α,12α-dihydroxy-5α-cholate | 1323923-39-2

• 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: benzyl 3α-butanoyloxy-7α,12α-dihydroxy-5α-cholate
• CAS: 1323923-39-2
• 化学式: C₃₅H₅₂O₆
• 分子量: 568.794
• InChiKey: FSFGOQYSBGSIDE-JMTGRPNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.46
• 重原子数：
  41.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  93.06
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  benzyl 3α-butanoyloxy-7α,12α-dihydroxy-5α-cholate 在 calcium hydride 、 palladium 10% on activated carbon 、 ammonium acetate 、 水 、 苄基三乙基溴化铵 、 potassium hydrogencarbonate 、 sodium hydroxide 作用下， 以 甲醇 、 异丙醇 、 甲苯 为溶剂， 反应 6.33h， 生成
  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 吡啶 、 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 benzyl 3α-butanoyloxy-7α,12α-dihydroxy-5α-cholate
  参考文献：
  名称：

  肠道共生体通过次级胆汁酸生物合成途径缓解 MASH

  摘要：

  研究发现肠道微生物群在代谢功能障碍相关脂肪性肝炎（MASH）的进展中发挥着重要作用，但其机制尚未确定。在这里，通过开发基于点击化学的富集策略，我们鉴定了几种微生物衍生的胆汁酸，包括以前未表征的3-琥珀酰胆酸（3-sucCA），它与肝组织患者的肝损伤呈负相关。 -活检证实的代谢功能障碍相关的脂肪肝病（MAFLD）。通过筛选人类细菌分离株，我们确定了能够有效生产 3-sucCA 和 3-sucCA 的菌株。通过基于活性的蛋白质纯化和鉴定，我们鉴定了一种负责 3-sucCA 生物合成的酶，注释为 β-内酰胺酶。此外，我们发现 3-sucCA 是一种流明限制代谢物，可通过促进 的生长来缓解 MASH。总之，我们的数据提供了对肠道微生物群-肝脏轴的新见解，可用于增强 MASH 的管理。

  DOI：

  10.1016/j.cell.2024.03.034