6-Benzyloxy-9-[(1S,2R,3S)-2,3-bis-(tert-butyl-dimethyl-silanyloxymethyl)-cyclopropylmethyl]-9H-purin-2-ylamine | 205323-54-2

• 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: 6-Benzyloxy-9-[(1S,2R,3S)-2,3-bis-(tert-butyl-dimethyl-silanyloxymethyl)-cyclopropylmethyl]-9H-purin-2-ylamine
• CAS: 205323-54-2
• 化学式: C₃₀H₄₉N₅O₃Si₂
• 分子量: 583.922
• InChiKey: FUPJRRWTXRMBIL-JOZNFPNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.89
• 重原子数：
  40.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  97.31
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  6-Benzyloxy-9-[(1S,2R,3S)-2,3-bis-(tert-butyl-dimethyl-silanyloxymethyl)-cyclopropylmethyl]-9H-purin-2-ylamine 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Novel Acyclic Nucleosides:  Discovery of a Cyclopropyl Nucleoside with Potent Inhibitory Activity against Herpesviruses

  摘要：

  A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized stal ting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 mu g/mL against HSV-1 Tomioka vs 0.81 mu g/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.

  DOI：

  10.1021/jm9705869
• 作为产物：
  描述：

  (1R,2S,3R)-2,3-Bis-(tert-butyl-dimethyl-silanyloxymethyl)-cyclopropanecarboxylic acid ethyl ester 在 lithium aluminium tetrahydride 、 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 6-Benzyloxy-9-[(1S,2R,3S)-2,3-bis-(tert-butyl-dimethyl-silanyloxymethyl)-cyclopropylmethyl]-9H-purin-2-ylamine
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Novel Acyclic Nucleosides:  Discovery of a Cyclopropyl Nucleoside with Potent Inhibitory Activity against Herpesviruses

  摘要：

  A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized stal ting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 mu g/mL against HSV-1 Tomioka vs 0.81 mu g/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.

  DOI：

  10.1021/jm9705869