24-methyl 3α-azido-7β-hydroxy-5β-cholanoate | 1364279-41-3

• 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-azido-7β-hydroxy-5β-cholanoate
• 英文别名: methyl 3α-azido-7β-hydroxy-5β-cholan-24-oate
• CAS: 1364279-41-3
• 化学式: C₂₅H₄₁N₃O₃
• 分子量: 431.619
• InChiKey: OCPWSSCYDOGFCX-ZQMFMVRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  95.29
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  24-methyl 3α-azido-7β-hydroxy-5β-cholanoate 在 水 、 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 21.0h， 以94%的产率得到3α-azido-7β-hydroxy-5β-cholan-24-oic acid
  参考文献：
  名称：

  结合三唑部分的核苷-胆汁酸的合理设计用于抗癌评估和SAR探索。

  摘要：

  本文中，我们报告了通过将2'-脱氧腺苷，2'-脱氧鸟苷，2'-脱氧尿苷以及腺苷和鸟苷衍生物与化学-，尿嘧啶-氨基磺酸酯结合而制备的核苷-胆汁酸缀合物文库的合成和生物学评估。 ，通过点击反应，去甲壳基，去甲壳基，去甲磺基和牛磺去氧胆酸衍生物。在体外针对白血病K562和HCT116结肠癌以及在正常成纤维细胞上测试了结合有三唑部分的新的核苷-胆汁酸缀合物。六种化合物对所选的癌症细胞系表现出令人感兴趣的抗增殖活性，对正常的成纤维细胞没有细胞毒性作用。还研究了可能的结构活性关系。

  DOI：

  10.3390/molecules22101710
• 作为产物：
  描述：

  甲基3,7-二羟基胆烷-24-酸酯 在 咪唑 、 sodium azide 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 24-methyl 3α-azido-7β-hydroxy-5β-cholanoate
  参考文献：
  名称：

  与1,2,3-三唑连接的脱氧腺苷-胆汁酸缀合物的 合成及体外细胞毒性

  摘要：

  我们在这里报告了通过1,2,3-三唑环连接的新型脱氧核苷-胆汁酸缀合物的合成和生物学评估。通过Cu（I）介导的3-叠氮胆酸衍生物和与脱氧腺苷的C-8位相连的末端炔基部分的1，3-偶极环加成反应（“点击”化学）合成了缀合物。在体外评估了所有新分子对四种人类细胞系（即白血病T Jurkat和K562；结肠癌HCT116；和卵巢癌A2780）的抗增殖活性以及对人成纤维细胞的细胞毒性。几种缀合物显示出对人白血病T细胞的强抗增殖活性。观察到最佳的细胞毒性两种白血病细胞系上的HdA-CDC的IC 50最高为8.51μM。还确定了几种缀合物的凋亡活性。

  DOI：

  10.1039/c3nj00513e

文献信息

• Fluorous-tag assisted synthesis of bile acid–bisphosphonate conjugates via orthogonal click reactions: an access to potential anti-resorption bone drugs
  作者：Chiara Massarenti、Olga Bortolini、Giancarlo Fantin、Dario Cristofaro、Daniele Ragno、Daniela Perrone、Elena Marchesi、Gianluca Toniolo、Alessandro Massi

  DOI：10.1039/c7ob00774d

  日期：——

  candidates is reported. The disclosed methodology relied on the installation of azide and thiol functionalities at the head and tail positions, respectively, of the BA scaffold and its subsequent decoration by orthogonal click reactions (copper-catalyzed azide–alkyne cycloaddition, thiol–ene or thiol–yne coupling) to introduce BP units and a fluorophore. Because of the troublesome isolation of the target

  据报道，合成了少量新的胆汁酸-双膦酸盐（BA-BP）偶联物作为潜在的候选药物。所披露的方法分别依赖于BA支架的头尾位置上的叠氮化物和硫醇官能团的安装以及随后通过正交点击反应（铜催化的叠氮化物-炔环加成，硫醇-烯或硫醇-炔偶联）的修饰）引入BP单元和荧光团。由于通过标准程序难以分离靶标结合物，因此该方法最终以具有轻质荧光标签的BA支架功能化，从而通过荧光固相萃取快速有效地纯化中间体和最终产物。
• Dihydroartemisinin–Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity
  作者：Elena Marchesi、Nicola Chinaglia、Massimo L. Capobianco、Paolo Marchetti、Tzu‐En Huang、Hao‐Cheng Weng、Jih‐Hwa Guh、Lih‐Ching Hsu、Daniela Perrone、Maria Luisa Navacchia

  DOI：10.1002/cmdc.201800756

  日期：2019.4.3

  on natural products-bile acids and dihydroartemisinin-were prepared by different synthetic methodologies and investigated for their in vitro biological activity against HL-60 leukemia and HepG2 hepatocellular carcinoma cell lines. Most of these hybrids presented significantly improved antiproliferative activities with respect to dihydroartemisinin and the parent bile acid. The two most potent hybrids

  通过不同的合成方法制备了一系列基于天然产物胆汁酸和双氢青蒿素的杂化化合物，并研究了它们对 HL-60 白血病和 HepG2 肝细胞癌细胞系的体外生物活性。这些杂种中的大多数在双氢青蒿素和母体胆汁酸方面表现出显着改善的抗增殖活性。该系列的两个最有效的杂交体在 HL-60 和 HepG2 细胞中表现出相对于单独的双氢青蒿素的细胞毒活性分别增加了 10.5 倍和 15.4 倍。通过流式细胞术分析和蛋白质印迹分析获得了熊去氧胆酸杂合体诱导细胞凋亡的有力证据。
• New fluorescent bile acids: Synthesis, chemical characterization, and disastereoselective uptake by Caco-2 cells of 3-deoxy 3-NBD-amino deoxycholic and ursodeoxycholic acid
  作者：Ferenc Májer、Johanna J. Salomon、Ruchika Sharma、Simona V. Etzbach、Mohd Nadzri Mohd Najib、Ray Keaveny、Aideen Long、Jun Wang、Carsten Ehrhardt、John F. Gilmer

  DOI：10.1016/j.bmc.2012.01.002

  日期：2012.3

  Deoxycholic acid (DCA), a secondary bile acid (BA), and ursodeoxycholic acid (UDCA), a tertiary BA, cause opposing effects in vivo and in cell suspensions. Fluorescent analogues of DCA and UDCA could help investigate important questions about their cellular interactions and distribution.We have prepared a set of isomeric 3 alpha- and 3 beta-amino analogues of UDCA and DCA and derivatised these with the discrete fluorophore, 4-nitrobenzo-2-oxa-1,3-diazol (NBD), forming the corresponding four fluorescent adducts. These absorb in the range 465-470 nm and fluoresce at approx. 535 nm.In order to determine the ability of the new fluorescent bile acids to mimic the parents, their uptake was studied using monolayers of Caco-2 cells, which are known to express multiple proteins of the organic anion-transporting peptide (OATP) subfamily of transporters. Cellular uptake was monitored over time at 4 and 37 degrees C to distinguish between passive and active transport.All four BA analogues were taken up but in a strikingly stereo-and structure-specific manner, suggesting highly discriminatory interactions with transporter protein(s). The alpha-analogues of DCA and to a lesser extent UDCA were actively transported, whereas the beta-analogues were not. The active transport process was saturable, with Michaelis-Menten constants for 3 alpha-NBD DCA (5) being K-m = 42.27 +/- 12.98 mu M and V-max = 2.8 +/- 0.4 nmol/(mg protein*min) and for 3 alpha-NBD UDCA (3) K-m = 28.20 +/- 7.45 mu M and V-max = 1.8 +/- 0.2 nmol/(mg protein(*)min). These fluorescent bile acids are promising agents for investigating questions of bile acid biology and for detection of bile acids and related organic anion transport processes. (C) 2012 Elsevier Ltd. All rights reserved.