acyclovir-5'-(phenyl methoxy-L-alaninyl)phosphate | 273928-30-6

• 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-5'-(phenyl methoxy-L-alaninyl)phosphate
• 英文别名: 9-[[[[(phenoxyl-1-methoxylcarbonylethylamino)phosphoryl]oxyl]ethoxyl]methyl]guanine；methyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-phenoxy-phosphoryl]amino]propanoate；methyl (2S)-2-[[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 273928-30-6
• 化学式: C₁₈H₂₃N₆O₇P
• 分子量: 466.39
• InChiKey: BETCLGGVEPGHNZ-QRPOTFRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  168
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  acyclovir-5'-(phenyl methoxy-L-alaninyl)phosphate 在 pig liver esterase 作用下， 以 丙酮 为溶剂， 反应 21.0h， 生成 (S)-2-{[2-(2-Amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethoxy]-hydroxy-phosphorylamino}-propionic acid
  参考文献：
  名称：

  Synthesis and antiviral activity of acyclovir-5′-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug

  摘要：

  We describe a synthesis of acyclovir-5'-(phenyl methoxy alaninyl) phosphate (2) from acyclovir (1). This compound was designed to act as a lipophilic, membrane-soluble prodrug of the free nucleotide. However, the biological activities of this derivative against a range of viruses indicated poor intracellular phosphate delivery, in marked contrast to the earlier successful delivery of several dideoxy anti-HIV nucleotides. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00061-5
• 作为产物：
  描述：

  阿昔洛韦 在 N-甲基咪唑 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 丙醇 为溶剂， 生成 acyclovir-5'-(phenyl methoxy-L-alaninyl)phosphate
  参考文献：
  名称：

  Synthesis and antiviral activity of acyclovir-5′-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug

  摘要：

  We describe a synthesis of acyclovir-5'-(phenyl methoxy alaninyl) phosphate (2) from acyclovir (1). This compound was designed to act as a lipophilic, membrane-soluble prodrug of the free nucleotide. However, the biological activities of this derivative against a range of viruses indicated poor intracellular phosphate delivery, in marked contrast to the earlier successful delivery of several dideoxy anti-HIV nucleotides. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00061-5

文献信息

• 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.
• COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRAL INFECTION
  申请人：Margolis Leonid

  公开号：US20110184003A1

  公开（公告）日：2011-07-28

  The invention relates to compounds and methods for treating or preventing a viral infection, by administering a monophosphorylated prodrug of acyclovir or monophosphorylated derivative of an acyclovir prodrug to a subject suffering from or susceptible (to a viral infection, such as HIV infection.
• US8946243B2
  申请人：——

  公开号：US8946243B2

  公开（公告）日：2015-02-03
• Synthesis and antiviral activity of acyclovir-5′-(phenyl methoxy alaninyl) phosphate as a possible membrane-soluble nucleotide prodrug
  作者：Christopher McGuigan、Martin J. Slater、Nigel R. Parry、Alex Perry、Sarah Harris

  DOI：10.1016/s0960-894x(00)00061-5

  日期：2000.4

  We describe a synthesis of acyclovir-5'-(phenyl methoxy alaninyl) phosphate (2) from acyclovir (1). This compound was designed to act as a lipophilic, membrane-soluble prodrug of the free nucleotide. However, the biological activities of this derivative against a range of viruses indicated poor intracellular phosphate delivery, in marked contrast to the earlier successful delivery of several dideoxy anti-HIV nucleotides. (C) 2000 Elsevier Science Ltd. All rights reserved.