3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester | 124930-59-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester
• 英文别名: 3'-azido-3'-deoxythymidine 5'-(hydrogen phosphonate)；3'-azido-3'-deoxythymidine 5'-hydrogenphosphonate；phosphazid；5'-(H-phosphonate) AZT；nikavir；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxyphosphinic acid
• CAS: 124930-59-2
• 化学式: C₁₀H₁₄N₅O₆P
• 分子量: 331.225
• InChiKey: HXXOFKXVESEZNB-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.21
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  159.38
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester 在 吡啶 、 RPMI 1640 、 N,N-二异丙基乙胺 、 氯磷酸二苯酯 、 fetal bovine serum 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 0.5h， 生成
  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
• 作为产物：
  描述：

  司他夫定 在 吡啶 、 potassium phosphate 、 三氯化磷 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 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

文献信息

• Aryl <i>H-</i>Phosphonates 17: (<i>N-</i>Aryl)phosphoramidates of Pyrimidine Nucleoside Analogues and Their Synthesis, Selected Properties, and Anti-HIV Activity
  作者：Joanna Romanowska、Michał Sobkowski、Agnieszka Szymańska-Michalak、Krystian Kołodziej、Aleksandra Dąbrowska、Andrzej Lipniacki、Andrzej Piasek、Zofia M. Pietrusiewicz、Marek Figlerowicz、Andrzej Guranowski、Jerzy Boryski、Jacek Stawiński、Adam Kraszewski

  DOI：10.1021/jm2001103

  日期：2011.10.13

  for the preparation of nucleoside 5′-(N-aryl)phosphoramidate monoesters 4 was developed. It consisted of a condensation of the corresponding nucleoside 5′-H-phosphonates with aromatic- or heteroaromatic amines promoted by diphenyl phosphorochloridate, followed by oxidation of the produced H-phosphonamidates with iodine/water. 5′-(N-Aryl)phosphoramidate monoesters derived from 3′-azido-3′-deoxythymidine

  开发了用于制备核苷5'-（N-芳基）氨基磷酸酯单酯4的新的合成方案。它由相应的核苷5'- H-膦酸酯与二苯基磷酸氯酯促进的芳族或杂芳族胺缩合，然后用碘/水氧化生成的H-膦酰胺酸酯。5′-（氮评估了衍生自3'-叠氮基3'-脱氧胸苷（AZT）或2'，3'-二脱氧尿苷（ddU）核苷以及各种芳香族和杂芳香族胺的-芳基）磷酸氨基甲酸酯单酯作为潜在的抗HIV药物。已发现这些化合物最有可能充当前核苷酸，并且其中一些具有优于参考AZT的治疗指数。
• Synthesis of AZT/d4T Boranophosphates as Anti-HIV Prodrug Candidates
  作者：Hua Fu、Yufen Zhao、Changxue Lin、Guangzhong Tu

  DOI：10.1055/s-2004-815939

  日期：——

  AZT/d4T phosphonates were synthesized by sequential condensation of AZT/d4T with the corresponding alcohols or 5′-DMT-thymidine in the presence of pivaloyl chloride. Sequential silylation, boronation, and hydrolysis in ammonium hydroxide of these phosphonates led to anti-HIV prodrug candidates AZT/d4T boranophosphates.

  AZT/d4T膦酸盐是通过在异戊酰氯存在下，依次将AZT/d4T与相应的醇或5′-DMT胸苷缩合合成的。这些膦酸盐依次进行硅烷化、硼化及在氨水中水解，得到抗HIV前药候选物AZT/d4T硼膦酸盐。
• Studies on the decomposition pathways of diastereoisomeric mixtures of aryl nucleoside α-hydroxyphosphonates under hydrolytic conditions. Synthesis of α-hydroxyphosphonate monoesters
  作者：Agnieszka Szymańska-Michalak、Jacek Stawiński、Adam Kraszewski

  DOI：10.1039/b9nj00717b

  日期：——

  mixtures) bearing different aryl groups, both in the ester and the hydroxymethine fragment, were investigated under various hydrolytic conditions. We found that in aqueous basic media, the stability and decomposition pathways of these compounds were governed by the electronic features of the aryl group in the hydroxymethine moiety (hydroxyphosphonate ⇌ H-phosphonate diester + aldehyde equilibria) and

  在各种水解条件下，研究了酯和羟基次甲基片段中带有不同芳基 的核苷α-羟基膦酸酯1（非对映异构混合物）的分解途径。我们发现，在碱性水溶液中，这些化合物的稳定性和分解途径受羟基次甲基部分中芳基的电子特征支配（羟基膦酸酯 ⇌ H-膦酸酯二酯+醛平衡）和攻击亲核试剂（α-亲核试剂，例如 次碘酸盐或过氧化物阴离子）。在hydroxyphosphonates的水解速率中观察到的差异显著1与它们的直径： -acylated衍生物指向由相邻的羟基功能施加的分子内酸催化的重要性。基于这些发现，为其他方面难以访问的有效合成协议羟基膦酸酯已经开发出类型7的单酯。
• <i>S</i>-Acyl-2-Thioethyl Aryl Phosphotriester Derivatives of AZT:  Synthesis, Antiviral Activity, and Stability Study
  作者：Suzanne Peyrottes、Gaëlle Coussot、Isabelle Lefebvre、Jean-Louis Imbach、Gilles Gosselin、Anne-Marie Aubertin、Christian Périgaud

  DOI：10.1021/jm021016y

  日期：2003.2.1

  The synthesis, antiviral activity, and stability study of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing modified l-tyrosinyl residues are reported. These compounds were obtained via phosphoramidite (P(III)) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors

  报道了带有修饰的1-酪氨酸残基的3'-叠氮基2'，3'-二脱氧胸苷（AZT）的磷酸三酯衍生物的合成，抗病毒活性和稳定性研究。这些化合物是通过亚磷酰胺（P（III））化学方法从适当的芳基前体获得的。评估了所有衍生物的体外抗HIV活性，在各种细胞培养实验中，它们似乎都是HIV-1复制的有效抑制剂，EC（50）值介于微摩尔和纳摩尔之间，尤其是在胸苷激酶中缺陷（TK（-））细胞，显示其充当单核苷酸前药的能力。这些混合的单核苷芳基磷酸三酯的拟议分解过程依次涉及酯酶和磷酸二酯酶的水解。
• Carbonylbisphosphonate and (diazomethylene)bisphosphonate analogues of AZT 5′-diphosphate
  作者：Charles E McKenna、Boris A Kashemirov、Christian N Rozé

  DOI：10.1016/s0045-2068(02)00521-7

  日期：2002.12

  A novel nucleotide analogue is described, in which the alpha,beta-phosphoric anhydride oxygen of a nucleoside 5(')-diphosphate is replaced by a carbonyl group: the carbonylbisphosphonate analogue 5 of 2('),3(')-dideoxy-3(')-azidothymidine 5(')-diphosphate (AZT 5(')-diphosphate). 5 was synthesized from tetramethyl (diazomethylene)bisphosphonate 1 via the trimethyl ester 4 of the corresponding AZT 5(

  描述了一种新的核苷酸类似物，其中核苷5（'）-二磷酸的α，β-磷酸酐氧被羰基取代：2（'），3（'）-二脱氧-的羰基双膦酸酯类似物5 3（'）-叠氮胸苷5（'）-二磷酸酯（AZT 5（'）-二磷酸酯）。通过相应的AZT 5（′）-（重氮亚甲基）双膦酸酯6的三甲酯4，由（重氮亚甲基）双膦酸酯四甲酯合成5，这也是一种新型的核苷酸类似物。通过反相HPLC分离出最终产物5，并通过31P，13C和1H NMR进行了表征。并通过高分辨率质谱分析。酮基5为可见发色团（黄色），可逆地形成无色水合物。当存在过量的镁离子时，酮水合物“ pK”为约4.2。