acyclovir-[1-naphthyl(benzoxy-L-alaninyl)]phosphate | 1059580-98-1

• 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: acyclovir-[1-naphthyl(benzoxy-L-alaninyl)]phosphate
• 英文别名: benzyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-(1-naphthyloxy)phosphoryl]amino]propanoate；benzyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
• CAS: 1059580-98-1
• 化学式: C₂₈H₂₉N₆O₇P
• 分子量: 592.548
• InChiKey: QCKXBZMJIKXFPM-QXHVSYNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  N(2)-DMFacyclovir-[1-naphthyl(benzoxy-L-alaninyl)]phosphate 以 异丙醇 为溶剂， 反应 48.0h， 以35%的产率得到acyclovir-[1-naphthyl(benzoxy-L-alaninyl)]phosphate
  参考文献：
  名称：

  Successful kinase bypass with new acyclovir phosphoramidate prodrugs

  摘要：

  Novel phosphoramidates of acyclovir have been prepared and evaluated in vitro against acyclovir-sensitive and -resistant herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV). Unlike the parent nucleoside these novel phosphate prodrugs retain antiviral potency versus the ACV-resistant virus strain, suggesting an efficient bypass of the viral thymidine kinase. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.069

文献信息

• Successful kinase bypass with new acyclovir phosphoramidate prodrugs
  作者：Christopher McGuigan、Marco Derudas、Joachim J. Bugert、Graciela Andrei、Robert Snoeck、Jan Balzarini

  DOI：10.1016/j.bmcl.2008.06.069

  日期：2008.8

  Novel phosphoramidates of acyclovir have been prepared and evaluated in vitro against acyclovir-sensitive and -resistant herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV). Unlike the parent nucleoside these novel phosphate prodrugs retain antiviral potency versus the ACV-resistant virus strain, suggesting an efficient bypass of the viral thymidine kinase. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.
• The Application of Phosphoramidate Protide Technology to Acyclovir Confers Anti-HIV Inhibition
  作者：Marco Derudas、Davide Carta、Andrea Brancale、Christophe Vanpouille、Andrea Lisco、Leonid Margolis、Jan Balzarini、Christopher McGuigan

  DOI：10.1021/jm9007856

  日期：2009.9.10

  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.