1-(6-(3-ethyl-thiourea)pyrimidine-4-yl)-1H-imidazole-4-carboxylic acid methylester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(6-(3-ethyl-thiourea)pyrimidine-4-yl)-1H-imidazole-4-carboxylic acid methylester
• 英文别名: methyl 1-(6-(3-ethylthioureido)pyrimidin-4-yl)-1H-imidazole-4-carboxylate；Methyl 1-[6-(ethylcarbamothioylamino)pyrimidin-4-yl]imidazole-4-carboxylate；methyl 1-[6-(ethylcarbamothioylamino)pyrimidin-4-yl]imidazole-4-carboxylate
• 化学式: C₁₂H₁₄N₆O₂S
• 分子量: 306.348
• InChiKey: UHFBVGJEZMXMOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  咪唑-4-甲酸甲酯 在 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.5h， 生成 1-(6-(3-ethyl-thiourea)pyrimidine-4-yl)-1H-imidazole-4-carboxylic acid methylester
  参考文献：
  名称：

  Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents

  摘要：

  Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, Sr, IC50 = 0.204 mu M, SI > 196; St, IC50 = 0.067 mu M, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced A beta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound Sr displayed appropriate blood brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of, scopolamine-induced amnesia mice. The multifunctional profiles of Sr and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease.

  DOI：

  10.1021/acs.jmedchem.6b00636

文献信息

• Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents
  作者：Xiaokang Li、Huan Wang、Zhengyu Lu、Xinyu Zheng、Wei Ni、Jin Zhu、Yan Fu、Fulin Lian、Naixia Zhang、Jian Li、Haiyan Zhang、Fei Mao

  DOI：10.1021/acs.jmedchem.6b00636

  日期：2016.9.22

  Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, Sr, IC50 = 0.204 mu M, SI > 196; St, IC50 = 0.067 mu M, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced A beta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound Sr displayed appropriate blood brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of, scopolamine-induced amnesia mice. The multifunctional profiles of Sr and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease.