6-[3-(benzyloxy)-2-(benzyloxymethyl)propyl]-4-methoxy-1,5-dimethylpyrimidin-2(1H)-one | 1312992-32-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-[3-(benzyloxy)-2-(benzyloxymethyl)propyl]-4-methoxy-1,5-dimethylpyrimidin-2(1H)-one
• CAS: 1312992-32-7
• 化学式: C₂₅H₃₀N₂O₄
• 分子量: 422.524
• InChiKey: KIFBUAXOOCMNOO-UHFFFAOYSA-N

物化性质

• 沸点：
  544.1±60.0 °C(predicted)
• 密度：
  1.11±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  31.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.58
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  6-[3-(benzyloxy)-2-(benzyloxymethyl)propyl]-4-methoxy-1,5-dimethylpyrimidin-2(1H)-one 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到6-[3-hydroxy-2-(hydroxymethyl)propyl]-4-methoxy-1,5-dimethylpyrimidin-2(1H)-one
  参考文献：
  名称：

  Synthesis, Crystal Structure, and in Vitro Biological Evaluation of C-6 Pyrimidine Derivatives: New Lead Structures for Monitoring Gene Expression in Vivo

  摘要：

  Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to ogold standardo 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (Km = 10 +/- 0.3 M; kcat = 0.036 +/- 0.015 sec-1). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues.

  DOI：

  10.1080/15257770.2011.581258
• 作为产物：
  描述：

  5,6-二甲基尿嘧啶 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲苯 、 乙腈 为溶剂， 反应 125.5h， 生成 6-[3-(benzyloxy)-2-(benzyloxymethyl)propyl]-4-methoxy-1,5-dimethylpyrimidin-2(1H)-one
  参考文献：
  名称：

  Synthesis, Crystal Structure, and in Vitro Biological Evaluation of C-6 Pyrimidine Derivatives: New Lead Structures for Monitoring Gene Expression in Vivo

  摘要：

  Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to ogold standardo 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (Km = 10 +/- 0.3 M; kcat = 0.036 +/- 0.015 sec-1). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues.

  DOI：

  10.1080/15257770.2011.581258