benzyl ((2-((2-(((dimethylamino)methylene)amino)-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy)ethoxy)(4-fluorophenoxy)phosphoryl)-L-alaninate | 1184942-69-5

• 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: benzyl ((2-((2-(((dimethylamino)methylene)amino)-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy)ethoxy)(4-fluorophenoxy)phosphoryl)-L-alaninate
• CAS: 1184942-69-5
• 化学式: C₂₇H₃₁FN₇O₇P
• 分子量: 615.558
• InChiKey: GKDSKHUYWUXSGR-UHHUWSAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  43.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  162.26
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  benzyl ((2-((2-(((dimethylamino)methylene)amino)-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy)ethoxy)(4-fluorophenoxy)phosphoryl)-L-alaninate 以 异丙醇 为溶剂， 反应 24.0h， 以16%的产率得到benzyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-(4-fluorophenoxy)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
• 作为产物：
  描述：

  4-fluoro-phenyl-(benzoxy-L-alaninyl)-phosphorochloridate 、 2-(N′,N′-dimethylformamidino)-9-[(2-hydroxyethoxy)methyl]-6-oxopurine 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 以52%的产率得到benzyl ((2-((2-(((dimethylamino)methylene)amino)-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy)ethoxy)(4-fluorophenoxy)phosphoryl)-L-alaninate
  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