1-((Z)-4-Hydroxy-2-hydroxymethyl-but-2-enyl)-5-methyl-1H-pyrimidine-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-((Z)-4-Hydroxy-2-hydroxymethyl-but-2-enyl)-5-methyl-1H-pyrimidine-2,4-dione
• 英文别名: 1-[(Z)-4-hydroxy-2-(hydroxymethyl)but-2-enyl]-5-methyl-pyrimidine-2,4-dione；1-[(Z)-4-hydroxy-2-(hydroxymethyl)but-2-enyl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₀H₁₄N₂O₄
• 分子量: 226.232
• InChiKey: JTXUOOIUNQSJOS-WAPJZHGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (Z)-1-{4-(benzoyloxy)-2-[(benzoyloxy)methyl]-2-buten-1-yl}thymine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以80%的产率得到1-((Z)-4-Hydroxy-2-hydroxymethyl-but-2-enyl)-5-methyl-1H-pyrimidine-2,4-dione
  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