4-(methylthio)phenyl bis<(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl> phosphate | 125440-26-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 4-(methylthio)phenyl bis<(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl> phosphate
• 英文别名: 4-(methylthio)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate；bis[[(2R,3S,5R)-5-[5-[(E)-2-bromoethenyl]-2,4-dioxopyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl] (4-methylsulfanylphenyl) phosphate
• CAS: 125440-26-8
• 化学式: C₂₉H₃₁Br₂N₄O₁₂PS
• 分子量: 850.432
• InChiKey: OJHAQCRZDCHAAA-JPPWVOQMSA-N

物化性质

• 密度：
  1.81±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  228
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4-(methylthio)phenyl bis<(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl> phosphate 在 间氯过氧苯甲酸 作用下， 以 乙醇 为溶剂， 以70%的产率得到4-(methylsulfonyl)phenyl bis<(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl> phosphate
  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
• 作为产物：
  描述：

  4-(methylthio)phenyl phosphorodichloridate 在 N-甲基咪唑 、 potassium carbonate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 20.0h， 生成 4-(methylthio)phenyl bis<(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl> phosphate
  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：——