24-methyl 3α-(methylsulfonyl)oxy-7β-acetoxy-5β-cholanoate | 936215-34-8

• 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: 24-methyl 3α-(methylsulfonyl)oxy-7β-acetoxy-5β-cholanoate
• CAS: 936215-34-8
• 化学式: C₂₈H₄₆O₇S
• 分子量: 526.735
• InChiKey: KSEVAFYJVSEKSI-AUEDEMTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.12
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  95.97
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  24-methyl 3α-(methylsulfonyl)oxy-7β-acetoxy-5β-cholanoate 在 吡啶 、 硝酸 、 potassium hydroxide 作用下， 以 甲醇 、 乙酸酐 为溶剂， 反应 4.0h， 生成 (R)-4-((3R,5R,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-(4-(nitrooxy)butoxy)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
  参考文献：
  名称：

  Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both NO carrier and targeting ligand

  摘要：

  Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-O-hydroxyl alkyl derivatives, with the intact 24-COOH being preserved for hepatocyte specific recognition. Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride. The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change. Co-administration of ursodeoxycholic acid (UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e. (C) 2014 Hui-Fen Wang and Bo-Hua Zhong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2014.04.001
• 作为产物：
  描述：

  3alpha,7beta-二-O-乙酰基乌苏基脱氧胆酸甲酯 在 吡啶 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 24-methyl 3α-(methylsulfonyl)oxy-7β-acetoxy-5β-cholanoate
  参考文献：
  名称：

  Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both NO carrier and targeting ligand

  摘要：

  Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-O-hydroxyl alkyl derivatives, with the intact 24-COOH being preserved for hepatocyte specific recognition. Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride. The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change. Co-administration of ursodeoxycholic acid (UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e. (C) 2014 Hui-Fen Wang and Bo-Hua Zhong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2014.04.001

文献信息

• Bile acid toxicity structure–activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)
  作者：Ruchika Sharma、Ferenc Majer、Vijaya Kumar Peta、Jun Wang、Ray Keaveney、Dermot Kelleher、Aideen Long、John F. Gilmer

  DOI：10.1016/j.bmc.2010.07.030

  日期：2010.9

  The molecular mechanisms and interactions underlying bile acid cytotoxicity are important to understand for intestinal and hepatic disease treatment and prevention and the design of bile acid-based therapeutics.Bile acid lipophilicity is believed to be an important cytotoxicity determinant but the relationship is not well characterized. In this study we prepared new azido and other lipophilic BAs and altogether assembled a panel of 37 BAs with good dispersion in lipophilicity as reflected in RPTLC R-Mw. The MTT cell viability assay was used to assess cytotoxicity over 24 h in the HET-1A cell line (oesophageal). RMw values inversely correlated with cell viability for the whole set (r(2) = 0.6) but this became more significant when non-acid compounds were excluded (r(2) = 0.82, n = 29). The association in more homologous subgroups was stronger still (r(2) > 0.96). None of the polar compounds were cytotoxic at 500 mu M, however, not all lipophilic BAs were cytotoxic. Notably, apart from the UDCA primary amide, lipophilic neutral derivatives of UDCA were not cytotoxic. Finally, CDCA, DCA and LagoDCA were prominent outliers being more toxic than predicted by R-Mw. In a hepatic carcinoma line, lipophilicity did not correlate with toxicity except for the common naturally occurring bile acids and their conjugates. There were other significant differences in toxicity between the two cell lines that suggest a possible basis for selective cytotoxicity. The study shows: (i) azido substitution in BAs imparts lipophilicity and toxicity depending on orientation and ionizability; (ii) there is an inverse correlation between R-Mw and toxicity that has good predictive value in homologous sets; (iii) lipophilicity is a necessary but apparently not sufficient characteristic for BA cytocidal activity to which it appears to be indirectly related. (C) 2010 Elsevier Ltd. All rights reserved.