3'-azidothymidine 5'-[p-methoxyphenyl methoxyalaninyl phosphate] | 149560-32-7

• 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'-azidothymidine 5'-[p-methoxyphenyl methoxyalaninyl phosphate]
• 英文别名: 3'-azido-3'-deoxythymidine-5'-(p-methoxyphenyl-methoxyalaninyl phosphate；3'-azidothymidine 5'-(p-methoxyphenyl methoxyalaninyl phosphate)；O(4MeOPh)-N(MeOCOEt)PO3NH AZT；methyl (2S)-2-[[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-(4-methoxyphenoxy)phosphoryl]amino]propanoate
• CAS: 149560-32-7
• 化学式: C₂₁H₂₇N₆O₉P
• 分子量: 538.454
• InChiKey: BTLBYQQAWSMQOX-RADHGCGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  3'-azidothymidine 5'-[p-methoxyphenyl methoxyalaninyl phosphate] 生成 3'-azido-3'-deoxythymidine-5'-methoxyalaninyl phosphate
  参考文献：
  名称：

  Cytotoxic nucleoside analog compound 003 for treating cancer

  摘要：

  本发明提供了一种制剂，包括化合物003或其代谢物与一种或多种羧酯酶抑制剂的组合。本发明提供了一种通过给予化合物003或其代谢物来抑制与增殖性细胞疾病相关的细胞增殖的方法。本发明还提供了一种阻止细胞周期的方法。本发明还描述了通过给予化合物003来抑制癌细胞增殖的治疗癌症的方法。

  公开号：

  US20060046972A1
• 作为产物：
  描述：

  p-methoxyphenyl dichlorophosphite 在 N-氯代丁二酰亚胺 、 三乙胺 、 叔丁醇 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 3'-azidothymidine 5'-[p-methoxyphenyl methoxyalaninyl phosphate]
  参考文献：
  名称：

  作为抗 HIV 前药的 AZT/d4T 芳基磷酰胺衍生物的一锅法合成

  摘要：

  芳基二氯化磷与一当量 AZT 或 d4T 和一当量叔丁醇的混合物的 Arbuzov 反应产生相应的 AZT/d4T 芳基 H-膦酸二酯，H-膦酸二酯与氨基酸甲酯的以下反应N-氯-琥珀酰亚胺 (NCS) 的存在以良好的产率产生了膜溶性抗 HIV 前药 AZT/d4T 芳基氨基磷酸酯衍生物。

  DOI：

  10.1055/s-2005-917085

文献信息

• Aryl phosphate derivatives of d4T having anti-HIV activity
  申请人：Parker Hughes Institute

  公开号：US06350736B1

  公开（公告）日：2002-02-26

  Aryl phosphate derivatives of d4T with para-bromo substitution on the aryl group show markedly increased potency as anti-HIV agents without undesirable levels of cytotoxic activity. In particular, these derivatives are potent inhibitors of HIV reverse transcriptase. In a preferred aspect of the present invention, the phosphorus of the aryl phosphate group is further substituted with an amino acid residue that may be esterified or substituted, such as a methoxy alaninyl group.

  d4T的芳基磷酸酯衍生物，在芳基上对位溴取代，显示出明显增强的抗HIV活性，而无不良水平的细胞毒活性。特别是，这些衍生物是HIV反转录酶的强效抑制剂。在本发明的首选方面，芳基磷酸酯基的磷进一步取代为氨基酸残基，该残基可以酯化或取代，如甲氧基丙氨基基团。
• Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT
  作者：Christopher McGuigan、Ranjith N. Pathirana、Jan Balzarini、Erik De Clercq

  DOI：10.1021/jm00060a013

  日期：1993.4

  Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective anti-HIV activity in CEM cells; the magnitude of the biological effect varied considerably depending on the nature of the phosphate blocking group. Moreover, several of the compounds retain marked antiviral activity iri TK- (thymidine kinase-deficient) mutant CEM cells in which AZT was virtually inactive. These data strongly support the hypothesis that the AZT phosphate derivatives exert their biological effects via intracellular release of AZT nucleotide forms and suggest that the potential of nucleoside drugs in antiviral chemotherapy may be enhanced by suitable nucleotide delivery strategies.
• Effect of change in nucleoside structure on the activation and antiviral activity of phosphoramidate derivatives
  作者：T.K. Venkatachalam、P. Samuel、S. Qazi、F.M. Uckun

  DOI：10.1016/j.bmc.2005.04.083

  日期：2005.9

  Changing the nucleoside group of a series of phosphoramidate derivatives affects the enzyme mediated hydrolysis rate of the compounds. d4T and AZT-substituted analogs were activated by enzymes such as lipases, esterases, and proteases. On the other hand, 3dT-substituted derivatives were comparatively less prone to hydrolysis under similar experimental conditions. From the experimental results, we propose that-the most preferable nucleoside group for enzyme activation is d4T rather than AZT or 3dT. Additionally, we also observed that depending on the enzymes used the chiral selectivity of the enzymes for the phosphorus center of these phosphoramidate derivatives differed, demonstrating the importance of the nucleoside structure for this class of compounds. (c) 2005 Elsevier Ltd. All rights reserved.
• One-Pot Synthesis of Aryl Phosphoramidate Derivatives of AZT/d4T as Anti-HIV Prodrugs
  作者：Hua Fu、Peng Jiang、Xin Guo、Yuyang Jiang、Yufen Zhao

  DOI：10.1055/s-2005-917085

  日期：——

  Arbuzov reaction of aryl phosphorodichloridite with mixture of one equivalent of AZT or d4T and one equivalent of tert-butyl alcohol led to the corresponding AZT/d4T aryl H-phosphonate diesters, and the following reactionof the H-phosphonate diesters with amino acid methyl esters in the presence of N-chloro-succinimide (NCS) produced membrane-soluble anti-HIV prodrugs AZT/d4T aryl phosphoramidate derivatives

  芳基二氯化磷与一当量 AZT 或 d4T 和一当量叔丁醇的混合物的 Arbuzov 反应产生相应的 AZT/d4T 芳基 H-膦酸二酯，H-膦酸二酯与氨基酸甲酯的以下反应N-氯-琥珀酰亚胺 (NCS) 的存在以良好的产率产生了膜溶性抗 HIV 前药 AZT/d4T 芳基氨基磷酸酯衍生物。
• Cytotoxic nucleoside analog compound 003 for treating cancer
  申请人：Uckun M. Fatih

  公开号：US20060046972A1

  公开（公告）日：2006-03-02

  The present invention provides pharmaceutical compositions comprising Compound 003 or metabolites thereof in combination with one or more carboxylesterase inhibitors. The invention provides methods for inhibiting cellular proliferation associated with proliferative cell disorders in a subject by administering Compound 003 or metabolites thereof. The invention also provides methods for arresting the cell cycle. Methods of inhibiting proliferation of cells for treatment of cancer by administering Compound 003 are described.

  本发明提供了一种制剂，包括化合物003或其代谢物与一种或多种羧酯酶抑制剂的组合。本发明提供了一种通过给予化合物003或其代谢物来抑制与增殖性细胞疾病相关的细胞增殖的方法。本发明还提供了一种阻止细胞周期的方法。本发明还描述了通过给予化合物003来抑制癌细胞增殖的治疗癌症的方法。