methyl 3-O-acetyl-7-O-mesylchenodeoxycholate | 81857-23-0

• 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: methyl 3-O-acetyl-7-O-mesylchenodeoxycholate
• 英文别名: methyl (4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3-acetyloxy-10,13-dimethyl-7-methylsulfonyloxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 81857-23-0
• 化学式: C₂₈H₄₆O₇S
• 分子量: 526.735
• InChiKey: ZUGSNLUMBHQGGX-XPIXAVGJSA-N

物化性质

• 沸点：
  597.3±33.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 3-O-acetyl-7-O-mesylchenodeoxycholate 在 甲醇 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 乙酸乙酯 为溶剂， 反应 128.0h， 生成 3α-hydroxy-7β-acetamido-5β-cholanoate
  参考文献：
  名称：

  [EN] COMPOUNDS FOR USE IN THE TREATMENT OF LIVER DISEASE
  [FR] COMPOSÉS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT D'UNE HÉPATOPATHIE

  摘要：

  本文揭示了胆酸衍生物的制造方法和用途。这些胆酸衍生物已经显示出作为治疗肝病的药物的潜力。

  公开号：

  WO2021032648A1
• 作为产物：
  描述：

  鹅脱氧胆酸甲酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 methyl 3-O-acetyl-7-O-mesylchenodeoxycholate
  参考文献：
  名称：

  衍生自脱氧胆酸，鹅去氧胆酸和石胆酸的新型高毒性胆汁酸

  摘要：

  为了研究3-叠氮基和24-酰胺化双重取代的作用，我们制备了一组由23种DCA，鹅去氧胆酸（CDCA）和石胆酸（LCA）的BA衍生物组成的新研究小组，在我们以前的研究中，这些特征分别与细胞毒性有关工作。使用3- [4,5-二甲基噻唑-2-基] -2,5-二苯基四唑溴化物（MTT）分析研究了化合物对HT-1080和Caco-2细胞活力的影响。为了了解细胞死亡的机制，使用流式细胞仪对具有降低细胞活力的高潜力化合物进行了进一步研究。用低微摩尔IC 50鉴定了几种化合物降低Caco-2和HT1080细胞系中细胞活力的数值，使其成为迄今报道的最有效的BA细胞凋亡因子之一。没有证据表明总体疏水性和细胞毒性之间存在联系，这支持了BA诱导细胞死亡可能是结构特异性的观点。衍生自DCA的化合物通过凋亡导致细胞死亡。有一些证据表明所研究的两种细胞系之间的选择性可能是由于CD95 / FAS的表达不同所致。毒性更大

  DOI：

  10.1016/j.bmc.2013.11.029

文献信息

• Potential bile acid metabolites. 6. Stereoisomeric 3,7-dihydroxy-5.beta.-cholanic acids
  作者：Takashi Iida、Frederic C. Chang

  DOI：10.1021/jo00136a030

  日期：1982.7
• 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.