(4R)-4-((3R,5R,10S,12S,13R,17R)-3-azido-12-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid | 1253736-49-0

• 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: (4R)-4-((3R,5R,10S,12S,13R,17R)-3-azido-12-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
• 英文别名: 3α-azido-12α-hydroxy-5β-cholanic acid；(4R)-4-[(3R,5R,8R,9S,10S,12S,13R,14S,17R)-3-azido-12-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 1253736-49-0
• 化学式: C₂₄H₃₉N₃O₃
• 分子量: 417.592
• InChiKey: ZBSOIMJHWBXZMM-LLQZFEROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  71.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-4-((3R,5R,10S,12S,13R,17R)-3-azido-12-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 氨 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 以37%的产率得到(4R)-4-((3R,5R,10S,12S,13R,17R)-3-azido-12-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide
  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
• 作为产物：
  描述：

  去氧胆酸 在 盐酸 、 N,N-二甲基丙烯基脲 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 高氯酸 、 碳酸氢钠 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 157.83h， 生成 (4R)-4-((3R,5R,10S,12S,13R,17R)-3-azido-12-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
  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

• Tripodal Bile Acid Architectures Based on a Triarylphosphine Oxide Core Obtained by Copper-Catalysed [1,3]-Dipolar Cycloaddition: Synthesis and Preliminary Aggregation Studies
  作者：Bala N. S. Thota、Aramballi J. Savyasachi、Nikolay Lukashev、Irina Beletskaya、Uday Maitra

  DOI：10.1002/ejoc.201301443

  日期：2014.3

  We report the synthesis and aggregation behaviour of new water-soluble, bile acid derived tripodal architectures based on a core derived from triphenylphosphine oxide. We employed the well-established copper-catalysed [1,3]-dipolar cycloaddition (CuAAC) for the construction of these tripodal molecules. The aggregation behaviour of these molecules in aqueous media was studied by different analytical

  我们报告了基于衍生自氧化三苯基膦的核心的新型水溶性、胆汁酸衍生的三足结构的合成和聚集行为。我们采用成熟的铜催化 [1,3]-偶极环加成 (CuAAC) 来构建这些三足分子。这些分子在水性介质中的聚集行为通过不同的分析方法进行研究，例如染料增溶、动态光散射、核磁共振和原子力显微镜。这些分子结构还提供了额外的优势，有助于理解胆汁酸骨架的性质和这些结构中类固醇 C-3 位置的构型的影响；据我们所知，这在文献中还没有报道。
• COMPOSITIONS AND METHODS FOR PROFILING OF GUT MICROBIOTA-ASSOCIATED BILE SALT HYDROLASE (BSH) ACTIVITY
  申请人：CORNELL UNIVERSITY

  公开号：US20210323996A1

  公开（公告）日：2021-10-21

  A composition having the following structure: wherein: R 1 is OH, ester group, ether group, amine, thiol, thioether, halide, or a group containing an alkynyl or azido functionality; R 2 is H, OH, ester group, ether group, amine, thiol, thioether, halide, or a group containing an alkynyl or azido functionality; R 3 is a group containing a reactive functionality capable of covalent binding to a thiol or amine; and R 4 is H, OH, ester group, ether group, amine, thiol, thioether, halide, or a group containing an alkynyl or azido functionality; wherein one of R 1 , R 2 and R 4 is a group containing an alkynyl or azido functionality. Also disclosed is a method for profiling changes in BSH enzyme activity by attaching active BSH enzymes in a sample to the probe shown above, attaching a tag to the probe, and detecting the active BSH enzymes to obtain an activity profile.

  一种具有以下结构的组合物：其中：R1为OH，酯基，醚基，胺，硫醇，硫醚，卤素，或含有炔基或叠氮功能的基团；R2为H，OH，酯基，醚基，胺，硫醇，硫醚，卤素，或含有炔基或叠氮功能的基团；R3为含有反应性功能的基团，能够共价结合到硫醇或胺上；R4为H，OH，酯基，醚基，胺，硫醇，硫醚，卤素，或含有炔基或叠氮功能的基团；其中R1、R2和R4中的一个为含有炔基或叠氮功能的基团。还公开了一种通过将样品中的活性BSH酶附着到上述探针上，将标记附着到探针上，并检测活性BSH酶以获得活性剖面的方法。
• 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.
• New highly toxic bile acids derived from deoxycholic acid, chenodeoxycholic acid and lithocholic acid
  作者：Ferenc Májer、Ruchika Sharma、Claire Mullins、Luke Keogh、Sinead Phipps、Shane Duggan、Dermot Kelleher、Stephen Keely、Aideen Long、Gábor Radics、Jun Wang、John F. Gilmer

  DOI：10.1016/j.bmc.2013.11.029

  日期：2014.1

  We have prepared a new panel of 23 BA derivatives of DCA, chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) in order to study the effect of dual substitution with 3-azido and 24-amidation, features individually associated with cytotoxicity in our previous work. The effect of the compounds on cell viability of HT-1080 and Caco-2 was studied using the 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium

  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