N(2)-acetyl-9-[2-(2-tetrahydrofuranyloxy)ethoxymethyl]guanine | 119282-50-7

• 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: N(2)-acetyl-9-[2-(2-tetrahydrofuranyloxy)ethoxymethyl]guanine
• 英文别名: Furavir；N-[6-oxo-9-[2-(oxolan-2-yloxy)ethoxymethyl]-1H-purin-2-yl]acetamide
• CAS: 119282-50-7
• 化学式: C₁₄H₁₉N₅O₅
• 分子量: 337.335
• InChiKey: GBSPXAZIJJPEIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  顺式-二氨基二硝酸基铂 、 N(2)-acetyl-9-[2-(2-tetrahydrofuranyloxy)ethoxymethyl]guanine 以 重水 为溶剂， 生成 cis-[Pt(NH3)2(Furavir)2](NO3)2
  参考文献：
  名称：

  Synthesis and characterisation of platinum(II) complexes with the antiviral agents Ftorafur and Furavir

  摘要：

  Novel hybrid drugs, [Pt(NH3)(2)(Ftorafur-H)(2)] (1) and [Pt(NH3)(2)(Furavir)(2)](NO3)(2) (2), have been prepared by reaction of Ftorafur (Ft) and Furavir (Fr) with cisplatin. Ftorafur, a prodrug of 5-fluorouracil containing a 2-tetrahydrofuranyl radical linked to N(1), is stable when coordinated to platinum through N(3) but the N(1)-furanyl bond is hydrolysed by platinum substrates (such as [Pt(NH3)(2)(H2O)(2)](2+) and [Pt(dien)(H2O)](2+)) in the free state. In contrast, Furavir, a derivative of N(2)-acetyl-acyclovir carrying a 2-tetrahydrofuranyl radical linked to the terminal part of the (2-oxy)-ethoxymethyl chain bound to N(9), when coordinated to platinum through N(7), readily undergoes hydrolysis of the O-furanyl bond releasing 2-hydroxytetrahydrofuran and leaving N(2)-acetyl-acyclovir coordinated to platinum. It is suggested that the hydrolysis of the X-furanyl bond (X = N or O for Ftorafur and Furavir, respectively), which is catalysed by Lewis acids, is favoured in the latter case by the long and flexible (2-oxy)-ethoxymethyl chain which allows the metal centre to reach over the furanyl moiety. This is not possible in the case of the Ftorafur derivative. This investigation has demonstrated the possibility of controlling the hydrolysis of a coordinated substrate in a multifunctional platinum drug by a suitable choice of the position of the breakable bond with respect to the metal centre. (C) 2001 Published by Elsevier Science B.V.

  DOI：

  10.1016/s0020-1693(01)00629-6

文献信息

• Synthesis and characterisation of platinum(II) complexes with the antiviral agents Ftorafur and Furavir
  作者：Angeliki Panagiotopoulou、Nikos Katsaros、Nicola G Di Masi、Giovanni Natile

  DOI：10.1016/s0020-1693(01)00629-6

  日期：2001.12

  Novel hybrid drugs, [Pt(NH3)(2)(Ftorafur-H)(2)] (1) and [Pt(NH3)(2)(Furavir)(2)](NO3)(2) (2), have been prepared by reaction of Ftorafur (Ft) and Furavir (Fr) with cisplatin. Ftorafur, a prodrug of 5-fluorouracil containing a 2-tetrahydrofuranyl radical linked to N(1), is stable when coordinated to platinum through N(3) but the N(1)-furanyl bond is hydrolysed by platinum substrates (such as [Pt(NH3)(2)(H2O)(2)](2+) and [Pt(dien)(H2O)](2+)) in the free state. In contrast, Furavir, a derivative of N(2)-acetyl-acyclovir carrying a 2-tetrahydrofuranyl radical linked to the terminal part of the (2-oxy)-ethoxymethyl chain bound to N(9), when coordinated to platinum through N(7), readily undergoes hydrolysis of the O-furanyl bond releasing 2-hydroxytetrahydrofuran and leaving N(2)-acetyl-acyclovir coordinated to platinum. It is suggested that the hydrolysis of the X-furanyl bond (X = N or O for Ftorafur and Furavir, respectively), which is catalysed by Lewis acids, is favoured in the latter case by the long and flexible (2-oxy)-ethoxymethyl chain which allows the metal centre to reach over the furanyl moiety. This is not possible in the case of the Ftorafur derivative. This investigation has demonstrated the possibility of controlling the hydrolysis of a coordinated substrate in a multifunctional platinum drug by a suitable choice of the position of the breakable bond with respect to the metal centre. (C) 2001 Published by Elsevier Science B.V.