[(2S,3R,5R)-5-(6-benzamidopurin-9-yl)-3-benzoyloxyoxolan-2-yl]methyl benzoate | 137157-37-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: [(2S,3R,5R)-5-(6-benzamidopurin-9-yl)-3-benzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 137157-37-0
• 化学式: C₃₁H₂₅N₅O₆
• 分子量: 563.569
• InChiKey: VOVOSFZEHZBAAM-DSNGMDLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N6-苯甲酰基腺嘌呤 、 3',5'-dibenzoyl-2'-deoxy-β-L-uridine 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 生成 [(2S,3R,5R)-5-(6-benzamidopurin-9-yl)-3-benzoyloxyoxolan-2-yl]methyl benzoate 、 3',5'-di-O-benzoyl-2'-deoxy-L-N⁶-benzoyladenosine
  参考文献：
  名称：

  L-Thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth

  摘要：

  We have demonstrated that herpes simplex 1 (HSV1) thymidine kinase (TK) shows no stereospecificity for D- and L-beta-nucleosides. In vitro, L enantiomers are not recognized by human TK, but function as specific substrates for the viral enzyme in the order: L-thymidine (L-T) much greater than 2'-deoxy-L-guanosine (L-dG) > 2'-deoxy-L-uridine (L-dU) > 2'-deoxy-L-cytidine (L-dC) > 2'-deoxy-L-adenosine (L-dA). HSV1 TK phosphorylates both thymidine enantiomers to their corresponding monophosphates with identical efficiency and the K(i) of L-T (2 muM) is almost identical to the K(m) for the natural substrate D-T (2.8 muM). The L enantiomer reduces the incorporation of exogenous [H-3]T into cellular DNA in HeLa TK-/HSV1 TK+ but not in wild-type HeLa cells, without affecting RNA, protein synthesis, cell growth, and viability. L-T markedly reduces HSV1 multiplication in HeLa cells. Our observations could lead to the development of a novel class of antiviral drugs characterized by low toxicity.

  DOI：

  10.1021/jm00100a029

文献信息

• L-Thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth
  作者：Silvio Spadari、Giovanni Maga、Federico Focher、Giovanni Ciarrocchi、Roberto Manservigi、Federico Arcamone、Massimo Capobianco、Antonio Carcuro、Francesco Colonna

  DOI：10.1021/jm00100a029

  日期：1992.10

  We have demonstrated that herpes simplex 1 (HSV1) thymidine kinase (TK) shows no stereospecificity for D- and L-beta-nucleosides. In vitro, L enantiomers are not recognized by human TK, but function as specific substrates for the viral enzyme in the order: L-thymidine (L-T) much greater than 2'-deoxy-L-guanosine (L-dG) > 2'-deoxy-L-uridine (L-dU) > 2'-deoxy-L-cytidine (L-dC) > 2'-deoxy-L-adenosine (L-dA). HSV1 TK phosphorylates both thymidine enantiomers to their corresponding monophosphates with identical efficiency and the K(i) of L-T (2 muM) is almost identical to the K(m) for the natural substrate D-T (2.8 muM). The L enantiomer reduces the incorporation of exogenous [H-3]T into cellular DNA in HeLa TK-/HSV1 TK+ but not in wild-type HeLa cells, without affecting RNA, protein synthesis, cell growth, and viability. L-T markedly reduces HSV1 multiplication in HeLa cells. Our observations could lead to the development of a novel class of antiviral drugs characterized by low toxicity.