6-chloro-1-(ethoxymethyl)pyrimidine-2,4(1H,3H)-dione | 1393847-13-6

• 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: 6-chloro-1-(ethoxymethyl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-chloro-1-(ethoxymethyl)uracil；6-Chloro-1-(ethoxymethyl)pyrimidine-2,4-dione
• CAS: 1393847-13-6
• 化学式: C₇H₉ClN₂O₃
• 分子量: 204.613
• InChiKey: HFPYYFCCJDYEEG-UHFFFAOYSA-N

物化性质

• 熔点：
  142-143 °C
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-1-(ethoxymethyl)pyrimidine-2,4(1H,3H)-dione 、 二苯二硫醚 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以84%的产率得到1-ethoxymethyl-6-(phenylthio)uracil
  参考文献：
  名称：

  Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

  摘要：

  New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2 {1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 mu g/mL; 0.046 mu M, SI > 1667) and (EC50 = 0.025 mu g/mL; 0.086 mu M, SI > 1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 mu g/ml; 3.27 mu M, SI > 25). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.038
• 作为产物：
  描述：

  6-氯尿嘧啶 、 氯甲基乙醚 在 N,O-双三甲硅基乙酰胺 作用下， 以 二氯甲烷 为溶剂， 以43.2 %的产率得到6-chloro-1-(ethoxymethyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  发现一类新的尿嘧啶衍生物作为潜在的混合谱系激酶域样蛋白 (MLK​​L) 抑制剂

  摘要：

  坏死性凋亡是程序性细胞死亡的一种形式。混合谱系激酶域样蛋白（MLKL）是坏死性凋亡的执行者，它参与多种疾病，如组织损伤和神经退行性疾病相关疾病。在这里，我们报告了通过支架变形从我们之前报道的黄嘌呤 MLKL 抑制剂 TC13172 开发出具有尿嘧啶核的新型 MLKL 抑制剂。经过合理的构效关系研究，我们得到了高效化合物56和66。机理研究表明，这些化合物部分抑制了 MLKL 寡聚化，并显着抑制了 MLKL 易位至膜。与 TC13172、56和66相比具有不同的作用方式，重要的是，它们与谷胱甘肽的反应速率低 150 倍以上。这种潜在脱靶效应和细胞毒性的降低使该系列成为进一步开发 MLKL 相关疾病治疗药物的有吸引力的起点。

  DOI：

  10.1021/acs.jmedchem.2c00548

文献信息

• Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors
  作者：Raimon Puig-de-la-Bellacasa、Laura Giménez、Sofia Pettersson、Rosalia Pascual、Encarna Gonzalo、José A. Esté、Bonaventura Clotet、José I. Borrell、Jordi Teixidó

  DOI：10.1016/j.ejmech.2012.04.038

  日期：2012.8

  New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 21,2,3,1} and 2 1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 mu g/mL; 0.046 mu M, SI > 1667) and (EC50 = 0.025 mu g/mL; 0.086 mu M, SI > 1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 mu g/ml; 3.27 mu M, SI > 25). (C) 2012 Elsevier Masson SAS. All rights reserved.
• Discovery of a New Class of Uracil Derivatives as Potential Mixed Lineage Kinase Domain-like Protein (MLKL) Inhibitors
  作者：Bo Cui、Bo Yan、Kang Wang、Lin Li、She Chen、Zhiyuan Zhang

  DOI：10.1021/acs.jmedchem.2c00548

  日期：2022.10.13

  programmed cell death. Mixed lineage kinase domain-like protein (MLKL) is the necroptosis executor, and it is involved in various diseases such as tissue damage and neurodegeneration-related diseases. Here, we report the development of novel MLKL inhibitors with a uracil nucleus through scaffold morphing from our previously reported xanthine MLKL inhibitor TC13172. After a rational structure–activity relationship

  坏死性凋亡是程序性细胞死亡的一种形式。混合谱系激酶域样蛋白（MLKL）是坏死性凋亡的执行者，它参与多种疾病，如组织损伤和神经退行性疾病相关疾病。在这里，我们报告了通过支架变形从我们之前报道的黄嘌呤 MLKL 抑制剂 TC13172 开发出具有尿嘧啶核的新型 MLKL 抑制剂。经过合理的构效关系研究，我们得到了高效化合物56和66。机理研究表明，这些化合物部分抑制了 MLKL 寡聚化，并显着抑制了 MLKL 易位至膜。与 TC13172、56和66相比具有不同的作用方式，重要的是，它们与谷胱甘肽的反应速率低 150 倍以上。这种潜在脱靶效应和细胞毒性的降低使该系列成为进一步开发 MLKL 相关疾病治疗药物的有吸引力的起点。