isopropyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-phenoxy-phosphoryl]amino]propanoate | 1184942-48-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: isopropyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-phenoxy-phosphoryl]amino]propanoate
• 英文别名: propan-2-yl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1184942-48-0
• 化学式: C₂₀H₂₇N₆O₇P
• 分子量: 494.444
• InChiKey: WHKGMFHCWIYDDP-NMFPIUAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  168
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  isopropyl ((2-((2-(((dimethylamino)methylene)amino)-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy)ethoxy)(phenoxy)phosphoryl)-L-alaninate 以 异丙醇 为溶剂， 反应 72.0h， 以7%的产率得到isopropyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-phenoxy-phosphoryl]amino]propanoate
  参考文献：
  名称：

  The Application of Phosphoramidate Protide Technology to Acyclovir Confers Anti-HIV Inhibition

  摘要：

  Recently, it has been reported that phosphorylated acyclovir (ACV) inhibits human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in a cell-free system. To deliver phosphorylated ACV inside cells, we designed ACV monophosphorylated derivatives using ProTide technology. We found that the L-alanine derived ProTides show anti-HIV activity at noncytotoxic concentrations; ester and aryl variation was tolerated, ACV ProTides with other amino acids, other than L-phenylalanine, showed no detectable activity against HIV in cell culture. The inhibitory activity of the prodrugs against herpes simplex virus (HSV) types-1 and -2 and thymidine kinase-deficient HSV-1 revealed different structure-activity relationships but was again consistent with successful nucleoside kinase bypass. Enzymatic and molecular modeling studies have been performed in order to better understand the antiviral behavior of these compounds. ProTides showing diminished carboxypeptidase lability translated to poor anti-HIV agents and vice versa, so the assay became predictive.

  DOI：

  10.1021/jm9007856

文献信息

• A mild and concise synthesis of aryloxy phosphoramidate prodrug of alcohols <i>via</i> transesterification reaction
  作者：Hanglu Ying、Jie Yao、Fan Wu、Yufen Zhao、Feng Ni

  DOI：10.1039/d2ra01995g

  日期：——

  A synthesis of aryloxy phosphoramidate prodrug of alcohols enabled by a transesterification strategy is described here. This reaction operates under mild conditions and thus has excellent functional group tolerance. This method provides an efficient and practical solution to the rapid construction of the aryloxy phosphoramidate prodrugs library for potential SAR studies.

  本文描述了通过酯交换策略实现醇的芳氧基氨基磷酸酯前药的合成。该反应在温和的条件下进行，因此具有优异的官能团耐受性。该方法为快速构建用于潜在S​​AR研究的芳氧基氨基磷酸酯前药库提供了有效且实用的解决方案。