5'-aminocarbonylphosphonyl-3'-azido-2',3'-dideoxythymidine | 725246-00-4

• 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: 5'-aminocarbonylphosphonyl-3'-azido-2',3'-dideoxythymidine
• 英文别名: 3'-azido-3'-deoxythymidine 5'-(aminocarbonyl)phosphonate；3'-azido-3'-deoxythymidine 5'-aminocarbonylphosphonate；5'-aminocarbonylphosphonyl-3'-azido-3'-deoxythymidine；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy-carbamoyl-phosphinic acid；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-carbamoylphosphinic acid
• CAS: 725246-00-4
• 化学式: C₁₁H₁₅N₆O₇P
• 分子量: 374.25
• InChiKey: YFAORDJHSLXZRZ-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  新戊醇 、 5'-aminocarbonylphosphonyl-3'-azido-2',3'-dideoxythymidine 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以54%的产率得到3'-azido-3'-deoxythymidine 5'-(2,2-dimethylpropyl) aminocarbonylphosphonate
  参考文献：
  名称：

  New Phosphonoformic Acid Derivatives of 3′-Azido-3′-Deoxythymidine

  摘要：

  New 5'-alkyl ethoxy- and aminocarbonylphosphonates of 3'-azido-3'-deoxythymidine (AZT) were synthesized, and their antiviral properties in HIV-1-infected cell cultures and stability to chemical hydrolysis were studied. The AZT 5'-aminocarbonylphosphonates were shown to be significantly more stable in phosphate buffer (pH 7.2) than the corresponding ethoxycarbonylphosphonates. The therapeutic (selectivity) index of some of the compounds exceeded that of the parent AZT due to their higher antiviral activity.

  DOI：

  10.1023/b:rubi.0000030131.37092.0a
• 作为产物：
  描述：

  齐多夫定 在 吡啶 、 ammonium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 反应 36.0h， 生成 5'-aminocarbonylphosphonyl-3'-azido-2',3'-dideoxythymidine
  参考文献：
  名称：

  Uncharged AZT and D4T Derivatives of Phosphonoformic and Phosphonoacetic Acids as Anti-HIV Pronucleosides

  摘要：

  Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.

  DOI：

  10.1021/jm0310176

文献信息

• 5′-Carbamoylphosphonyl-[6-3H]-AZT as a Tool for Studying Metabolic Transformations of the Nonradioactive Counterpart, an Inhibitor of HIV Replication
  作者：Dmitry V. Yanvarev、Elena A. Shirokova、Maria V. Astapova、Vyacheslav I. Shram、Marina K. Kukhanova、Yury S. Skoblov

  DOI：10.1080/15257770701505899

  日期：2007.11.26

  An effective synthesis of 5′-carbamoylphosphonyl-[6-3H]-AZT was developed from [6-3H]-AZT.For the synthesized compound, chemical and enzymatic stability were determined and its penetrationa cross HL-60 cell membranes was studied.

  以[6-3H]-AZT为原料开发了5′-氨基甲酰基膦酰基-[6-3H]-AZT的有效合成方法。对合成的化合物进行了化学稳定性和酶学稳定性测定，并研究了其对HL-60细胞膜的渗透性。
• New Lipophilic Derivatives of AZT and d4T 5′-Phosphonates
  作者：Elena A. Shirokova、Maxim V. Jasko、Anastasiya L. Khandazhinskaya、Dmitry V. Yanvarev、Yury S. Skoblov、Tatyana R. Pronayeva、Nina V. Fedyuk、Andrey G. Pokrovsky、Marina K. Kukhanova

  DOI：10.1081/ncn-120022718

  日期：2003.10

  5'-Aminocarbonylphosphonyl and aminocarbonylmethylphosphonyl diesters of AZT and d4T were synthesized as potential anti-HIV agents.
• Uncharged AZT and D4T Derivatives of Phosphonoformic and Phosphonoacetic Acids as Anti-HIV Pronucleosides
  作者：Elena A. Shirokova、Maxim V. Jasko、Anastasiya L. Khandazhinskaya、Alexander V. Ivanov、Dmitry V. Yanvarev、Yury S. Skoblov、Vladimir A. Mitkevich、Eduard V. Bocharov、Tatyana R. Pronyaeva、Nina V. Fedyuk、Marina K. Kukhanova、Andrey G. Pokrovsky

  DOI：10.1021/jm0310176

  日期：2004.7.1

  Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.
• New Phosphonoformic Acid Derivatives of 3′-Azido-3′-Deoxythymidine
  作者：E. A. Shirokova、M. V. Jasko、A. L. Khandazhinskaya、A. V. Ivanov、D. V. Yanvarev、Yu. S. Skoblov、T. R. Pronyaeva、N. V. Fedyuk、A. G. Pokrovskii、M. K. Kukhanova

  DOI：10.1023/b:rubi.0000030131.37092.0a

  日期：2004.5

  New 5'-alkyl ethoxy- and aminocarbonylphosphonates of 3'-azido-3'-deoxythymidine (AZT) were synthesized, and their antiviral properties in HIV-1-infected cell cultures and stability to chemical hydrolysis were studied. The AZT 5'-aminocarbonylphosphonates were shown to be significantly more stable in phosphate buffer (pH 7.2) than the corresponding ethoxycarbonylphosphonates. The therapeutic (selectivity) index of some of the compounds exceeded that of the parent AZT due to their higher antiviral activity.