1-{2-[2-(Benzyl-methyl-amino)-ethoxy]-ethyl}-3-pyridin-3-yl-thiourea

• 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-[2-(Benzyl-methyl-amino)-ethoxy]-ethyl}-3-pyridin-3-yl-thiourea
• 英文别名: 1-[2-[2-[benzyl(methyl)amino]ethoxy]ethyl]-3-pyridin-3-ylthiourea
• 化学式: C₁₈H₂₄N₄OS
• 分子量: 344.481
• InChiKey: ANNNAAMLISZACR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-<2-<2-(N-benzyl-N-methylamino)ethoxy>ethyl>-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-{2-[2-(Benzyl-methyl-amino)-ethoxy]-ethyl}-3-pyridin-3-yl-thiourea
  参考文献：
  名称：

  Flexible 1-[(2-Aminoethoxy)alkyl]-3-ar(o)yl(thio)ureas as Novel Acetylcholinesterase Inhibitors. Synthesis and Biochemical Evaluation

  摘要：

  A series of flexible 1-(2-aminoethoxy)-3-ar(o)yl(thio)ureas was synthesized and assessed for antiacetylcholinesterase activity. This series was designed in order to optimize the spacer length linking the two pharmacophoric moieties, i.e., the basic nitrogen and the ar(o)yl(thio)urea unit, and to test compounds with greater conformational flexibility. Thus, the replacement of the previously described spacer, 4-piperidinylethyl, by a linear ethoxyethyl chain gave compounds of slightly comparable potency, providing that they were correctly substituted. The results show that this new flexible spacer is compatible with high inhibitory activities. The optimal chain length corresponds to five methylene groups, allowing an efficient interaction between the two pharmacophoric units and the two reported hypothetical enzyme hydrophobic binding sites. Moreover, the initially optimized benzyl group, attached to the basic nitrogen, was found to be advantageously replaced by a cyclohexyl group, showing that an aromatic residue does not represent a prerequisite for activity.

  DOI：

  10.1021/jm00015a020

文献信息

• Flexible 1-[(2-Aminoethoxy)alkyl]-3-ar(o)yl(thio)ureas as Novel Acetylcholinesterase Inhibitors. Synthesis and Biochemical Evaluation
  作者：Jean-Louis Vidaluc、Francis Calmel、Dennis C. H. Bigg、Elisabeth Carilla、Mike Briley

  DOI：10.1021/jm00015a020

  日期：1995.7

  A series of flexible 1-(2-aminoethoxy)-3-ar(o)yl(thio)ureas was synthesized and assessed for antiacetylcholinesterase activity. This series was designed in order to optimize the spacer length linking the two pharmacophoric moieties, i.e., the basic nitrogen and the ar(o)yl(thio)urea unit, and to test compounds with greater conformational flexibility. Thus, the replacement of the previously described spacer, 4-piperidinylethyl, by a linear ethoxyethyl chain gave compounds of slightly comparable potency, providing that they were correctly substituted. The results show that this new flexible spacer is compatible with high inhibitory activities. The optimal chain length corresponds to five methylene groups, allowing an efficient interaction between the two pharmacophoric units and the two reported hypothetical enzyme hydrophobic binding sites. Moreover, the initially optimized benzyl group, attached to the basic nitrogen, was found to be advantageously replaced by a cyclohexyl group, showing that an aromatic residue does not represent a prerequisite for activity.