二[2-[(2-氨基-6-氧代-3H-嘌呤-9-基)甲氧基]乙基](4-甲基磺酰基苯基)磷酸酯 | 125440-27-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 二[2-[(2-氨基-6-氧代-3H-嘌呤-9-基)甲氧基]乙基](4-甲基磺酰基苯基)磷酸酯
• 英文名称: bis<2-(guanin-9-ylmethoxy)ethyl> 4-(methylsulfonyl)phenyl phosphate
• 英文别名: Bis(2-(guanin-9-ylmethoxy)ethoxy)-4-(methylsulfonyl)phenyl phosphate；bis[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethyl] (4-methylsulfonylphenyl) phosphate
• CAS: 125440-27-9
• 化学式: C₂₃H₂₇N₁₀O₁₀PS
• 分子量: 666.568
• InChiKey: CQBSOGFPVYFEBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  45
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  276
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  阿昔洛韦 、 4-(methylsulfonyl)phenyl phosphorodichloridate 在 N-甲基咪唑 作用下， 以 吡啶 为溶剂， 反应 2.0h， 以6%的产率得到二[2-[(2-氨基-6-氧代-3H-嘌呤-9-基)甲氧基]乙基](4-甲基磺酰基苯基)磷酸酯
  参考文献：
  名称：

  Synthesis and biological properties of novel phosphotriesters: a new approach to the introduction of biologically active nucleotides into cells

  摘要：

  A series of aryl bis(3'-O-acetylthymidin-5'-yl) phosphate derivatives have been synthesized in order to find a suitable aryl derivative which would hydrolyze to the bis(nucleosid-5'-yl) phosphate under physiological conditions. The 4-(methylsulfonyl)phenyl derivative was selected and 4-(methylsulfonyl)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate (6d) and bis[2-(guanin-9-ylmethoxy)ethoxy]-4-(methylsulfonyl)phenyl phosphate (7b) were prepared. The former compound (6d) was stable in human serum and only following hydrolysis to the 5'-5'-linked diester (half-life of 17 h at pH 7.7) was it enzymatically degraded very rapidly by phosphodiesterases. Compounds 6d and 7b were evaluated for antiherpesvirus effects, both in vitro and in vivo. Their antiviral spectrum and potency was remarkably similar to that of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)-methyl]guanine (ACV), suggesting that they only act as prodrugs of BVDU and ACV, respectively. However, compound 6d did show unexpected toxicity, which could be explained by the liberation of BVDUMP following penetration of the triester into the cell.

  DOI：

  10.1021/jm00167a019

文献信息

• FARROW, STUART N.;JONES, A. STANLEY;KUMAR, AJIT;WALKER, RICHARD T.;BALZAR+, J. MED. CHEM., 33,(1990) N, C. 1400-1406
  作者：FARROW, STUART N.、JONES, A. STANLEY、KUMAR, AJIT、WALKER, RICHARD T.、BALZAR+

  DOI：——

  日期：——
• Synthesis and biological properties of novel phosphotriesters: a new approach to the introduction of biologically active nucleotides into cells
  作者：Stuart N. Farrow、A. Stanley Jones、Ajit Kumar、Richard T. Walker、Jan Balzarini、Erik De Clercq

  DOI：10.1021/jm00167a019

  日期：1990.5

  A series of aryl bis(3'-O-acetylthymidin-5'-yl) phosphate derivatives have been synthesized in order to find a suitable aryl derivative which would hydrolyze to the bis(nucleosid-5'-yl) phosphate under physiological conditions. The 4-(methylsulfonyl)phenyl derivative was selected and 4-(methylsulfonyl)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate (6d) and bis[2-(guanin-9-ylmethoxy)ethoxy]-4-(methylsulfonyl)phenyl phosphate (7b) were prepared. The former compound (6d) was stable in human serum and only following hydrolysis to the 5'-5'-linked diester (half-life of 17 h at pH 7.7) was it enzymatically degraded very rapidly by phosphodiesterases. Compounds 6d and 7b were evaluated for antiherpesvirus effects, both in vitro and in vivo. Their antiviral spectrum and potency was remarkably similar to that of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)-methyl]guanine (ACV), suggesting that they only act as prodrugs of BVDU and ACV, respectively. However, compound 6d did show unexpected toxicity, which could be explained by the liberation of BVDUMP following penetration of the triester into the cell.