So221 | 142629-81-0

• 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: So221
• 英文别名: Azt-pmap；methyl (2S)-2-[[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 142629-81-0
• 化学式: C₂₀H₂₅N₆O₈P
• 分子量: 508.428
• InChiKey: CNUMCGXPKWOQFJ-FBXIHYFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  11

制备方法与用途

生物活性

Azt-pmap 是一种核苷类似物，具体为 AZT 的磷酸芳基衍生物。研究表明，Azt-pmap 具有抗 HIV 活性。AZT 作为用于治疗 HIV 感染的核苷逆转录酶抑制剂 (NRTI) 已被广泛使用。

靶点

目标
HIV-1

体外研究

Azt-pmap 在感染 C8166 和 JM 细胞中表现出抗 HIV-1 活性，EC₅₀ 值分别为 0.08 μM 和 0.32 μM。该化合物在上述细胞系中的毒性剂量（TC₅₀）分别为 500 μM。此外，Azt-pmap 还能抑制病毒复制。

反应信息

• 作为反应物：
  描述：

  So221 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Potential Multifunctional Inhibitors of HIV-1 Reverse Transcriptase. Novel [AZT]-[TSAO-T] and [d4T]-[TSAO-T] Heterodimers Modified in the Linker and in the Dideoxynucleoside Region

  摘要：

  In an attempt to combine the anti-HIV-inhibitory capacity of nucleoside reverse transcriptase (RT) inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI), several heterodimer analogues of the previously reported [AZT]-(CH(2))(3)-[TSAO-T] prototype have been prepared. In these novel series, other NRTIs, an expanded range of linkers with different conformational freedom and other attachment sites for these linkers on the base part of the NRTI analogue have been explored. Moreover, in order to circumvent the dependence of the NRTI moiety of the heterodimer an activation by cellular nucleoside kinases, novel heterodimers in which the NRTI is bearing a masked monophosphate group at the 5'-position are described. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable, or even superior, to that of the AZT heterodimer prototype. The nature of the NRTI was important far the eventual anti-HIV-1 activity. In particular, the d4T heterodimer derivative containing a propyl linker between the N-3 positions of the base of TSAO-T and d4T was similar to 5- to 10-fold more inhibitory to HIV-1 than the corresponding AZT heterodimer prototype.

  DOI：

  10.1021/jm991092+
• 作为产物：
  描述：

  二氯磷酸苯酯 在 N-甲基咪唑 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 So221
  参考文献：
  名称：

  Benyumov, Alexey O.; Venkatachalam, Taracad K.; Grigoriants, Olga O., Arzneimittel-Forschung/Drug Research, 2005, vol. 55, # 2, p. 114 - 122

  摘要：

  DOI：

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。
• 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。
• 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.
• Potential Multifunctional Inhibitors of HIV-1 Reverse Transcriptase. Novel [AZT]-[TSAO-T] and [d4T]-[TSAO-T] Heterodimers Modified in the Linker and in the Dideoxynucleoside Region
  作者：Sonsoles Velázquez、Victoria Tuñón、María Luisa Jimeno、Cristina Chamorro、Erik De Clercq、Jan Balzarini、María José Camarasa

  DOI：10.1021/jm991092+

  日期：1999.12.1

  In an attempt to combine the anti-HIV-inhibitory capacity of nucleoside reverse transcriptase (RT) inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI), several heterodimer analogues of the previously reported [AZT]-(CH(2))(3)-[TSAO-T] prototype have been prepared. In these novel series, other NRTIs, an expanded range of linkers with different conformational freedom and other attachment sites for these linkers on the base part of the NRTI analogue have been explored. Moreover, in order to circumvent the dependence of the NRTI moiety of the heterodimer an activation by cellular nucleoside kinases, novel heterodimers in which the NRTI is bearing a masked monophosphate group at the 5'-position are described. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable, or even superior, to that of the AZT heterodimer prototype. The nature of the NRTI was important far the eventual anti-HIV-1 activity. In particular, the d4T heterodimer derivative containing a propyl linker between the N-3 positions of the base of TSAO-T and d4T was similar to 5- to 10-fold more inhibitory to HIV-1 than the corresponding AZT heterodimer prototype.
• Benyumov, Alexey O.; Venkatachalam, Taracad K.; Grigoriants, Olga O., Arzneimittel-Forschung/Drug Research, 2005, vol. 55, # 2, p. 114 - 122
  作者：Benyumov, Alexey O.、Venkatachalam, Taracad K.、Grigoriants, Olga O.、Vassilev, Alexei O.、Tibbles, Heather E.、Downs, Suzanne、Dumez, Darin、Uckun, Fatih M.

  DOI：——

  日期：——