2-[(2-Amino-6-fluoro-9H-purin-9-yl)methoxy]ethyl 2-methylpropanoate | 220150-71-0

• 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: 2-[(2-Amino-6-fluoro-9H-purin-9-yl)methoxy]ethyl 2-methylpropanoate
• 英文别名: 2-[(2-amino-6-fluoropurin-9-yl)methoxy]ethyl 2-methylpropanoate
• CAS: 220150-71-0
• 化学式: C₁₂H₁₆FN₅O₃
• 分子量: 297.289
• InChiKey: LFJKMYVIFSZIMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-amino-6-chloro-9-<(2-hydroxyethoxy)methyl>-9H-purine 在 4-二甲氨基吡啶 、 potassium fluoride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， -78.0~80.0 ℃ 、5.33 kPa 条件下， 反应 123.33h， 生成 2-[(2-Amino-6-fluoro-9H-purin-9-yl)methoxy]ethyl 2-methylpropanoate
  参考文献：
  名称：

  Synthesis and evaluation of 2-amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine esters as potential prodrugs of acyclovir

  摘要：

  2-Amino -6-fluoro-9-(2-hydroxyethoxymethyl)purine (2) and its ester derivatives 4a-d were synthesized as potential prodrugs of acyclovir, and were evaluated for their oral acyclovir bioavailability in rats and in vivo antiviral efficacy in HSV-1-infected mice. Treatment of 2-amino-6-chloro-9-(2-hydroxyethoxymethy (3) with trimethylamine in THF/DMF (4:1) followed by a reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2 in 78% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)(2)O, (n-PrCO)(2)O, or (i-PrCO)(2)O) in DMF in the presence of a catalytic amount of DMAP at room temperature produced the esters 4a-d in 90-98% yields. Of the prodrugs tested in rats, the isobutyrate 4d achieved the highest mean urinary recovery of acyclovir (51%) that is 5.7-fold higher than that of acyclovir (9%) and comparable to that of valacyclovir (50%). The prodrug 4d protected dose-dependently the mortality of HSV-1-infected mice, and the group treated with 4d at a dose of 400 mg/kg showed the longest mean survival day (14.6 +/- 3.1 days) (mean +/- S.D.). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)80026-6

文献信息

• Synthesis and evaluation of 2-amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine esters as potential prodrugs of acyclovir
  作者：Dae-Kee Kim、Namkyu Lee、Guang-Jin Im、Hun-Taek Kim、Key H. Kim

  DOI：10.1016/s0968-0896(98)80026-6

  日期：1998.12

  2-Amino -6-fluoro-9-(2-hydroxyethoxymethyl)purine (2) and its ester derivatives 4a-d were synthesized as potential prodrugs of acyclovir, and were evaluated for their oral acyclovir bioavailability in rats and in vivo antiviral efficacy in HSV-1-infected mice. Treatment of 2-amino-6-chloro-9-(2-hydroxyethoxymethy (3) with trimethylamine in THF/DMF (4:1) followed by a reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2 in 78% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)(2)O, (n-PrCO)(2)O, or (i-PrCO)(2)O) in DMF in the presence of a catalytic amount of DMAP at room temperature produced the esters 4a-d in 90-98% yields. Of the prodrugs tested in rats, the isobutyrate 4d achieved the highest mean urinary recovery of acyclovir (51%) that is 5.7-fold higher than that of acyclovir (9%) and comparable to that of valacyclovir (50%). The prodrug 4d protected dose-dependently the mortality of HSV-1-infected mice, and the group treated with 4d at a dose of 400 mg/kg showed the longest mean survival day (14.6 +/- 3.1 days) (mean +/- S.D.). (C) 1998 Elsevier Science Ltd. All rights reserved.