3'-azido-2',3'-dideoxythymidine monophosphate | 29706-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3'-azido-2',3'-dideoxythymidine monophosphate
• 英文别名: Zidovudine monophosphate；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl dihydrogen phosphate
• CAS: 29706-85-2
• 化学式: C₁₀H₁₄N₅O₇P
• 分子量: 347.224
• InChiKey: OIFWQOKDSPDILA-XLPZGREQSA-N

物化性质

• 熔点：
  154-160°C (dec.)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热）、水（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  9

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R20/21/22
• 安全说明：
  S36

反应信息

• 作为反应物：
  描述：

  3'-azido-2',3'-dideoxythymidine monophosphate 在 吡啶 、 三氯化磷 作用下， 以 二氯甲烷 、 formamide 、 乙腈 为溶剂， 反应 3.0h， 生成 3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester
  参考文献：
  名称：

  P-(Alkyl)-Nucleoside 5′-Hydrogenphosphonates as Depot Forms of Antiviral Nucleotide Analogues

  摘要：

  P-(Alkyl)esters of AZT 5'-hydrogenphosphonate were synthesized and their stabilities in the phosphate buffer and human serum were evaluated. The esters bearing residues of primary and secondary alcohols were degraded to give AZT, whereas those containing tertiary alkyl groups yielded, AZT 5'-hydrogenphosphonate. The corresponding derivatives of d2A and d4T showed the same properties.

  DOI：

  10.1080/15257770008045461
• 作为产物：
  描述：

  3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester 在 吡啶 、 2,6-二甲基吡啶 、 三乙胺 、 氯磷酸二苯酯 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 1.08h， 生成 3'-azido-2',3'-dideoxythymidine monophosphate
  参考文献：
  名称：

  Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5′-α-hydroxyphosphonates

  摘要：

  Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosplionates 2 correlates well with the type and extent of their chemical or enzymatic degradation in Culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.048

文献信息

• Mononucleoside Phosphotriester Derivatives with S-Acyl-2-thioethyl Bioreversible Phosphate-Protecting Groups: Intracellular Delivery of 3'-Azido-2',3'-dideoxythymidine 5'-Monophosphate
  作者：Isabelle Lefebvre、Christian Perigaud、Alain Pompon、Anne-Marie Aubertin、Jean-Luc Girardet、Andre Kirn、Gilles Gosselin、Jean-Louis Imbach

  DOI：10.1021/jm00020a007

  日期：1995.9

  The synthesis, in vitro anti-HIV-1 activity, and decomposition pathways of several mononucleoside phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) incorporating a new kind of carboxylate esterase-labile transient phosphate-protecting group, namely, S-acyl-2-thioethyl, are reported. All the described compounds showed marked antiviral activity in thymidine kinase-deficient CEM cells

  3'-叠氮基2'，3'-二脱氧胸苷（AZT）的几种单核苷磷酸三酯衍生物的合成，体外抗HIV-1活性和分解途径，结合了一种新型的羧酸酯酶不稳定的瞬时磷酸保护基团据报道，即S-酰基-2-硫代乙基。所有描述的化合物在胸腺嘧啶激酶缺失的CEM细胞中均表现出显着的抗病毒活性，其中AZT实际上是无活性的。结果强烈支持这样的假说，即这种前核苷酸通过AZT的5'-单核苷酸的细胞内递送发挥其生物学作用。在细胞提取物和培养基中的分解研究证实了这一点。
• ANTIVIRAL COMPOUNDS AND COMPOSITIONS
  申请人：Quart Barry D.

  公开号：US20080249066A1

  公开（公告）日：2008-10-09

  Described herein are compounds useful in the treatment of viral diseases, compositions comprising them and methods of using them. The compounds comprise a nucleoside or nucleoside analog linked, commonly through a phosphate group to one of a selected group of lipids. In some embodiments, the compounds described herein are useful for treating HIV infection, AIDS and other viral infections.

  本文描述了用于治疗病毒性疾病的化合物，包括这些化合物的组合物以及使用它们的方法。这些化合物包括一个核苷或核苷类似物，通常通过磷酸酯基团连接到一组选定的脂质之一。在某些实施例中，本文描述的化合物可用于治疗HIV感染、艾滋病和其他病毒感染。
• Enzymatic Phosphorylation of Unnatural Nucleosides
  作者：Yiqin Wu、Ming Fa、Eunju Lee Tae、Peter G. Schultz、Floyd E. Romesberg

  DOI：10.1021/ja028050m

  日期：2002.12.1

  In an effort to expand the genetic alphabet, a number of unnatural, predominantly hydrophobic, nucleoside analogues have been developed which pair selectively in duplex DNA and during enzymatic synthesis. Significant progress has been made toward the efficient in vitro replication of DNA containing these base pairs. However, the in vivo expansion of the genetic alphabet will require that the unnatural

  为了扩大遗传字母表，已经开发了许多非天然的、主要是疏水性的核苷类似物，它们在双链 DNA 中和酶促合成过程中选择性地配对。在含有这些碱基对的 DNA 的体外有效复制方面取得了重大进展。然而，基因字母表的体内扩展将要求非天然三磷酸核苷在细胞内以足够的浓度用于 DNA 复制。我们报告了我们为开发基于核苷补救酶的非自然体内核苷磷酸化途径所做的初步努力。该途径的第一步由黑腹果蝇核苷激酶催化，该激酶催化核苷磷酸化为相应的单磷酸酯。
• LIPID CLEAVAGE ENZYME
  申请人：——

  公开号：US20020106363A1

  公开（公告）日：2002-08-08

  A membranous enzyme not yet described in the state-of-the-art can be extracted from cellular membrane fractions of blood leukocytes or monocytes/macrophages. Also disclosed is the use of substrates of this enzyme to prepare medicaments that contain these substrates as pharmaceutical active substance. These medicaments are useful to direct pharmacologically active substances to target cells and to enrich target cells with said substances. Also disclosed are in-vitro research systems containing this enzyme used to detect other substrates of this enzyme.

  一种尚未在现代技术中描述的膜酶可以从血液白细胞或单核/巨噬细胞的细胞膜分离物中提取。还公开了使用该酶底物制备含有这些底物作为药物活性成分的药物的用途。这些药物可用于将药理活性物质定向到目标细胞并用该物质富集目标细胞。还公开了含有该酶的体外研究系统，用于检测该酶的其他底物。
• A Tool for the Import of Natural and Unnatural Nucleoside Triphosphates into Bacteria
  作者：Aaron W. Feldman、Emil C. Fischer、Michael P. Ledbetter、Jen-Yu Liao、John C. Chaput、Floyd E. Romesberg

  DOI：10.1021/jacs.7b11404

  日期：2018.1.31

  Nucleoside triphosphates play a central role in biology, but efforts to study these roles have proven difficult because the levels of triphosphates are tightly regulated in a cell and because individual triphosphates can be difficult to label or modify. In addition, many synthetic biology efforts are focused on the development of unnatural nucleoside triphosphates that perform specific functions in

  三磷酸核苷在生物学中发挥着核心作用，但研究这些作用的努力已被证明是困难的，因为细胞中三磷酸的水平受到严格调控，而且单个三磷酸可能难以标记或修饰。此外，许多合成生物学工作都集中在开发在细胞环境中发挥特定功能的非天然三磷酸核苷。一般而言，将所需的三磷酸盐直接引入细胞的一般手段将促进这两种努力。以前，我们证明了来自三角褐指藻 (PtNTT2) 的核苷三磷酸转运蛋白在大肠杆菌中的重组表达，其功能是导入添加到培养基中的三磷酸。在这里，为了探索这种方法的普遍性和实用性，我们报告了 PtNTT2 的构效关系研究。我们使用传统的竞争性摄取抑制分析来表征核碱基、糖和三磷酸修饰的影响，然后开发 LC-MS/MS 分析以直接测量修饰对导入的影响。最后，我们使用转运蛋白导入放射性标记或 2'-氟修饰的三磷酸，并量化它们与 DNA 和 RNA 的结合。结果证明了 PtNTT2 介导的天然或修饰的三磷酸核苷导入对于不