1-(2-methoxyethyl)-6-(4-octylanilino)uracil

• 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: 1-(2-methoxyethyl)-6-(4-octylanilino)uracil
• 英文别名: 1-(2-Methoxyethyl)-6-(4-octylanilino)pyrimidine-2,4-dione
• 化学式: C₂₁H₃₁N₃O₃
• 分子量: 373.495
• InChiKey: ACNRTHBCFZXSKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-methoxyethyl)-6-(4-octylanilino)uracil 在 碘代三甲硅烷 作用下， 以 氯仿 为溶剂， 反应 4.0h， 以79%的产率得到1-(2-hydroxyethyl)-6-(4-octylanilino)uracil
  参考文献：
  名称：

  Molecular Modeling and Synthesis of Inhibitors of Herpes Simplex Virus Type 1 Uracil-DNA Glycosylase

  摘要：

  We recently reported the properties of the first selective inhibitors of herpes simplex virus type 1 (HSV1) uracil-DNA glycosylase (UDG), an enzyme of DNA repair that has been proposed to be required for reactivation of the virus from latency. 6-(4-Octylanilino)uracil (octAU) was the most potent inhibitor among a series of 6-(4-alkylanilino)uracils, acting in the micromolar range and without effect against human UDG. A 28.5-kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved. We have used the coordinates of this structure in order to study interaction of our inhibitors with the enzyme, and a model of binding between octAU and UDG has been derived. Starting with the optimized model, the activity of several octAU analogues was predicted, and the values compared favorably with experimental results found for the synthetic compounds. Several hydrophilic derivatives were predicted and found to be active as UDG inhibitors. These compounds will be useful to determine if UDG, like the viral thymidine kinase, is required for reactivation of HSV1 from latency in nerve cells.

  DOI：

  10.1021/jm980718d
• 作为产物：
  描述：

  4-octylaniline hydrochloride 、 6-氨基-1-(2-甲氧基-乙基)-1H-嘧啶-2,4-二酮 在 4-辛基苯胺 作用下， 反应 0.67h， 以85%的产率得到1-(2-methoxyethyl)-6-(4-octylanilino)uracil
  参考文献：
  名称：

  Molecular Modeling and Synthesis of Inhibitors of Herpes Simplex Virus Type 1 Uracil-DNA Glycosylase

  摘要：

  We recently reported the properties of the first selective inhibitors of herpes simplex virus type 1 (HSV1) uracil-DNA glycosylase (UDG), an enzyme of DNA repair that has been proposed to be required for reactivation of the virus from latency. 6-(4-Octylanilino)uracil (octAU) was the most potent inhibitor among a series of 6-(4-alkylanilino)uracils, acting in the micromolar range and without effect against human UDG. A 28.5-kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved. We have used the coordinates of this structure in order to study interaction of our inhibitors with the enzyme, and a model of binding between octAU and UDG has been derived. Starting with the optimized model, the activity of several octAU analogues was predicted, and the values compared favorably with experimental results found for the synthetic compounds. Several hydrophilic derivatives were predicted and found to be active as UDG inhibitors. These compounds will be useful to determine if UDG, like the viral thymidine kinase, is required for reactivation of HSV1 from latency in nerve cells.

  DOI：

  10.1021/jm980718d

文献信息

• US6177437B1
  申请人：——

  公开号：US6177437B1

  公开（公告）日：2001-01-23
• Molecular Modeling and Synthesis of Inhibitors of Herpes Simplex Virus Type 1 Uracil-DNA Glycosylase
  作者：Hongmao Sun、Chengxin Zhi、George E. Wright、Daniela Ubiali、Massimo Pregnolato、Annalisa Verri、Federico Focher、Silvio Spadari

  DOI：10.1021/jm980718d

  日期：1999.7.1

  We recently reported the properties of the first selective inhibitors of herpes simplex virus type 1 (HSV1) uracil-DNA glycosylase (UDG), an enzyme of DNA repair that has been proposed to be required for reactivation of the virus from latency. 6-(4-Octylanilino)uracil (octAU) was the most potent inhibitor among a series of 6-(4-alkylanilino)uracils, acting in the micromolar range and without effect against human UDG. A 28.5-kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved. We have used the coordinates of this structure in order to study interaction of our inhibitors with the enzyme, and a model of binding between octAU and UDG has been derived. Starting with the optimized model, the activity of several octAU analogues was predicted, and the values compared favorably with experimental results found for the synthetic compounds. Several hydrophilic derivatives were predicted and found to be active as UDG inhibitors. These compounds will be useful to determine if UDG, like the viral thymidine kinase, is required for reactivation of HSV1 from latency in nerve cells.