1-phenyl-3-(N-phenyl-4-methoxyphenylacetimidoyl)thiourea

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-phenyl-3-(N-phenyl-4-methoxyphenylacetimidoyl)thiourea
• 英文别名: (1E)-1-[anilino-(4-methoxyphenyl)methylidene]-3-phenylthiourea
• 化学式: C₂₁H₁₉N₃OS
• 分子量: 361.467
• InChiKey: HZERZOJQOXSUEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  77.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-phenyl-3-(N-phenyl-4-methoxyphenylacetimidoyl)thiourea 在 溴 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 12.0h， 以15%的产率得到3-(4-methoxyphenyl)-2-phenyl-5-phenylimino-2,5-dihydro-1,2,4-thiadiazole hydrobromide
  参考文献：
  名称：

  5-Imino-1,2,4-Thiadiazoles: First Small Molecules As Substrate Competitive Inhibitors of Glycogen Synthase Kinase 3

  摘要：

  Cumulative evidence strongly supports that glycogen synthase kinase-3 (GSK-3) is a pathogenic molecule when it is up-dysregulated, emerging as an important therapeutic target in severe unmet human diseases. GSK-3 specific inhibitors might be promising effective drugs for the treatment of devastating pathologies such as neurodegenerative diseases, stroke, and mood disorders. As GSK-3 has the ability to phosphorylate primed substrates, small molecules able to bind to this site should be perfect drug candidates, able to partially block the activity of the enzyme over some specific substrates. Here, we report substituted 5-imino-1,2,4-thiadiazoles as the first small molecules able to inhibit GSK-3 in a substrate competitive manner. These compounds are cell permeable, able to decrease inflammatory activation and to selectively differentiate neural stem cells. Overall, 5-imino-1,2,4-thiadiazoles are presented here as new molecules able to decrease neuronal cell death and to increase endogenous neurogenesis blocking the GSK-3 substrate site

  DOI：

  10.1021/jm201463v
• 作为产物：
  描述：

  N-苯基-4-甲氧基苯甲酰胺 在 氯化亚砜 作用下， 以 丙酮 为溶剂， 反应 4.0h， 生成 1-phenyl-3-(N-phenyl-4-methoxyphenylacetimidoyl)thiourea
  参考文献：
  名称：

  5-Imino-1,2,4-Thiadiazoles: First Small Molecules As Substrate Competitive Inhibitors of Glycogen Synthase Kinase 3

  摘要：

  Cumulative evidence strongly supports that glycogen synthase kinase-3 (GSK-3) is a pathogenic molecule when it is up-dysregulated, emerging as an important therapeutic target in severe unmet human diseases. GSK-3 specific inhibitors might be promising effective drugs for the treatment of devastating pathologies such as neurodegenerative diseases, stroke, and mood disorders. As GSK-3 has the ability to phosphorylate primed substrates, small molecules able to bind to this site should be perfect drug candidates, able to partially block the activity of the enzyme over some specific substrates. Here, we report substituted 5-imino-1,2,4-thiadiazoles as the first small molecules able to inhibit GSK-3 in a substrate competitive manner. These compounds are cell permeable, able to decrease inflammatory activation and to selectively differentiate neural stem cells. Overall, 5-imino-1,2,4-thiadiazoles are presented here as new molecules able to decrease neuronal cell death and to increase endogenous neurogenesis blocking the GSK-3 substrate site

  DOI：

  10.1021/jm201463v

文献信息

• Cycloaddition ofN-(2,2,2-trichloroethylidene)-substituted carboxamides and carbamates to 1,2,4-thiadiazol-5(2H)-imines
  作者：Vladimir S. Zyabrev、Mikhail A. Rensky、Eduard B. Rusanov、Boris S. Drach

  DOI：10.1002/hc.10182

  日期：——

  1,2,4-Thiadiazol-5(2H)-imines 4 react with N-(2,2,2-trichloroethylidene)-substituted amides 5 to form [3 + 2]-cycloaddition products 6 featured by an extra coordination of the ring sulfur atom to the terminal nitrogen atom of the side 1,3-diazapropenylidene group, as established by X-ray diffraction investigation. This coordination evidently plays an important role in the alkylation of compounds 6

  1,2,4-噻二唑-5(2H)-亚胺 4 与 N-(2,2,2-三氯亚乙基)-取代的酰胺 5 反应形成 [3 + 2]-环加成产物 6，其特征在于通过 X 射线衍射研究确定，环硫原子与 1,3-二氮杂亚丙基侧基的末端氮原子相连。这种配位显然在温和条件下在氧原子上将化合物 6 烷基化为 8 中起重要作用。SN 键“转换”恢复原来的 1,2,4-噻二唑环随之发生。© 2003 Wiley Periodicals, Inc. 杂原子化学 14:474–480, 2003; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.10182
• 5-Imino-1,2,4-Thiadiazoles: First Small Molecules As Substrate Competitive Inhibitors of Glycogen Synthase Kinase 3
  作者：Valle Palomo、Daniel I. Perez、Concepcion Perez、Jose A. Morales-Garcia、Ignacio Soteras、Sandra Alonso-Gil、Arantxa Encinas、Ana Castro、Nuria E. Campillo、Ana Perez-Castillo、Carmen Gil、Ana Martinez

  DOI：10.1021/jm201463v

  日期：2012.2.23

  Cumulative evidence strongly supports that glycogen synthase kinase-3 (GSK-3) is a pathogenic molecule when it is up-dysregulated, emerging as an important therapeutic target in severe unmet human diseases. GSK-3 specific inhibitors might be promising effective drugs for the treatment of devastating pathologies such as neurodegenerative diseases, stroke, and mood disorders. As GSK-3 has the ability to phosphorylate primed substrates, small molecules able to bind to this site should be perfect drug candidates, able to partially block the activity of the enzyme over some specific substrates. Here, we report substituted 5-imino-1,2,4-thiadiazoles as the first small molecules able to inhibit GSK-3 in a substrate competitive manner. These compounds are cell permeable, able to decrease inflammatory activation and to selectively differentiate neural stem cells. Overall, 5-imino-1,2,4-thiadiazoles are presented here as new molecules able to decrease neuronal cell death and to increase endogenous neurogenesis blocking the GSK-3 substrate site