9-(2-hydroxyethoxymethyl)guanine phosphoromonohexylamidate | 1400637-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-(2-hydroxyethoxymethyl)guanine phosphoromonohexylamidate
• 英文别名: N-hexyl-2-[(2-amino-6-oxo-3,6-dihydro-9H-purin-9-yl)methoxy]ethyl phosphoramidate ammonium salt；2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-N-hexylphosphonamidic acid;azane
• CAS: 1400637-42-4
• 化学式: C₁₄H₂₅N₆O₅P*H₃N
• 分子量: 405.394
• InChiKey: DIMINHLRQWCFMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.12
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  154
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-(2-hydroxyethoxymethyl)guanine phosphoromonohexylamidate 在 potassium dihydrogenphosphate 、 potassium hydroxide 作用下， 以 aq. phosphate buffer 、 水 为溶剂， 反应 120.0h， 生成 阿昔洛韦
  参考文献：
  名称：

  Phosphoramidate derivatives of acyclovir: Synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro

  摘要：

  The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 mu M. It also inhibited replication of wild-type HSV-1 (9.7 mu M) as well as an acyclovir-resistant strain (25 mu M). None of the synthesised compounds showed any cytotoxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.008
• 作为产物：
  描述：

  阿昔洛韦 在 磷酸三乙酯 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 生成 9-(2-hydroxyethoxymethyl)guanine phosphoromonohexylamidate
  参考文献：
  名称：

  Phosphoramidate derivatives of acyclovir: Synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro

  摘要：

  The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 mu M. It also inhibited replication of wild-type HSV-1 (9.7 mu M) as well as an acyclovir-resistant strain (25 mu M). None of the synthesised compounds showed any cytotoxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.008

文献信息

• Acyclovir phosphoramidates as potential anti-HIV drugs
  作者：N. F. Zakirova、I. L. Karpenko、M. M. Prokofjeva、C. Vanpouille、V. S. Prassolov、A. V. Shipitsyn、S. N. Kochetkov

  DOI：10.1007/s11172-014-0571-1

  日期：2014.5

  A number of phosphoramidate derivatives of acyclovir (ACV) were obtained. These compounds revealed themselves as latent forms of acyclovir monophosphate (ACV-MP). The optimized route to the title phosphoramidates involves the synthesis of intermediate phosphorodichloridates followed by their treatment with various amines. The compounds obtained showed moderate antiviral activity both in vitro in a

  获得了许多阿昔洛韦 (ACV) 的氨基磷酸酯衍生物。这些化合物表明它们是阿昔洛韦单磷酸酯 (ACV-MP) 的潜伏形式。标题氨基磷酸酯的优化路线包括合成中间体二氯化磷，然后用各种胺处理。获得的化合物在体外在安全筛选抗 HIV 试剂的受控系统和组织系统中均显示出中等的抗病毒活性，该组织系统能够在两周内对药物的效率及其对 HIV 复制的影响进行体外测定。