5-Nonyl-5-phenylimidazolidine-2,4-dione | 227181-20-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 5-Nonyl-5-phenylimidazolidine-2,4-dione
• CAS: 227181-20-6
• 化学式: C₁₈H₂₆N₂O₂
• 分子量: 302.417
• InChiKey: YDNZJQWFOGASIE-UHFFFAOYSA-N

物化性质

• 熔点：
  115-116 °C
• 密度：
  1.044±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-Nonyl-5-phenylimidazolidine-2,4-dione 在 盐酸 、 氢氧化钾 、 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 28.5h， 生成 2-amino-2-phenylundecanoic acid hydrochloride
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies for Hydantoins and Analogues as Voltage-Gated Sodium Channel Ligands

  摘要：

  We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing,an effective non-hydantoin ligand. To further understand structural features that result in optimum binding. here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [H-3]-batrachotoxinin A 20-a-benzoate ([H-3]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore. which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.

  DOI：

  10.1021/jm040077o
• 作为产物：
  描述：

  氰化钾 、 碳酸氢铵 、 四硝基苯氯甲酸酯 以 乙醇 、 水 为溶剂， 反应 12.0h， 以95%的产率得到5-Nonyl-5-phenylimidazolidine-2,4-dione
  参考文献：
  名称：

  乙内酰脲与神经元电压依赖性钠通道结合的比较分子场分析。

  摘要：

  比较分子场分析（CoMFA）是一种3-D QSAR技术，被广泛用于将生物学活性与空间和静电场中观察到的差异相关联。在这项研究中，CoMFA被用于基于14种结构多样的5-苯基乙内酰脲类似物生成一个模型，以描述对于增强钠通道结合很重要的结构和静电特征。通过体外钠通道结合活性的偏最小二乘（PLS）分析（表示为log IC50）和CoMFA描述符列进行关联，得出最终的非交叉验证模型，其训练集的R2 = 0.988。对于相同的训练集，最终的CoMFA模型比具有log P（R2 = 0.801）的简单关联更好地解释了数据。CoMFA的空间图和静电图描述了两个一般特征，这些特征可增强与钠通道的结合。这些包括优选的5-苯环取向和由C 5-烷基链产生的有利的空间效应。然后，利用该模型来准确预测乙内酰脲14-20的文献钠通道活性，但该组未包括在训练集中。最后，使用乙内酰脲CoMFA模型设计结构新颖的α-羟基-

  DOI：

  10.1021/jm980556l

文献信息

• Synthesis and Structure−Activity Relationship Studies for Hydantoins and Analogues as Voltage-Gated Sodium Channel Ligands
  作者：Congxiang Zha、George B. Brown、Wayne J. Brouillette

  DOI：10.1021/jm040077o

  日期：2004.12.1

  We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing,an effective non-hydantoin ligand. To further understand structural features that result in optimum binding. here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [H-3]-batrachotoxinin A 20-a-benzoate ([H-3]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore. which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.
• Comparative Molecular Field Analysis of Hydantoin Binding to the Neuronal Voltage-Dependent Sodium Channel
  作者：Milton L. Brown、Congxiang C. Zha、Christopher C. Van Dyke、George B. Brown、Wayne J. Brouillette

  DOI：10.1021/jm980556l

  日期：1999.5.1

  general features that result in enhanced binding to the sodium channel. These include a preferred 5-phenyl ring orientation and a favorable steric effect resulting from the C5-alkyl chain. This model was then utilized to accurately predict literature sodium channel activities for hydantoins 14-20, which were not included in the training set. Finally the hydantoin CoMFA model was used to design the structurally

  比较分子场分析（CoMFA）是一种3-D QSAR技术，被广泛用于将生物学活性与空间和静电场中观察到的差异相关联。在这项研究中，CoMFA被用于基于14种结构多样的5-苯基乙内酰脲类似物生成一个模型，以描述对于增强钠通道结合很重要的结构和静电特征。通过体外钠通道结合活性的偏最小二乘（PLS）分析（表示为log IC50）和CoMFA描述符列进行关联，得出最终的非交叉验证模型，其训练集的R2 = 0.988。对于相同的训练集，最终的CoMFA模型比具有log P（R2 = 0.801）的简单关联更好地解释了数据。CoMFA的空间图和静电图描述了两个一般特征，这些特征可增强与钠通道的结合。这些包括优选的5-苯环取向和由C 5-烷基链产生的有利的空间效应。然后，利用该模型来准确预测乙内酰脲14-20的文献钠通道活性，但该组未包括在训练集中。最后，使用乙内酰脲CoMFA模型设计结构新颖的α-羟基-