2-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione | 188914-67-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
• CAS: 188914-67-2
• 化学式: C₁₈H₂₄N₄O₃
• 分子量: 344.414
• InChiKey: KHJHWJODAPMNNX-UHFFFAOYSA-N

物化性质

• 沸点：
  491.4±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-碘戊烷 、 2-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 24.5h， 以56%的产率得到
  参考文献：
  名称：

  Synthesis and structure–activity relationships of a new model of arylpiperazines. Part 7: Study of the influence of lipophilic factors at the terminal amide fragment on 5-HT1A affinity/selectivity

  摘要：

  The influence of lipophilic factors at the amide fragment of a new series of (+/-)-7a-alkyl-2-[4-(4-arylpiperazin-1-yl)butyl]1,3-dioxoperhydropyrrolo[1,2-c]imidazoles 2 and of (+/-)-7a-alkyl-2-[(4-arylpiperazin-1-yl)methyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazoles 3 has been studied. Variations of logP have been carried out by introducing different hydrocarbonated substituents (R-1) at the position 7a of the bicyclohydantoin, namely the non-pharmacophoric part. All the new compounds exhibit high potency for the 5-HT1A receptor; however, affinities for the a, receptor are high for compounds 2a-l while compounds 3a-f are selective over this adrenergic receptor. On the other hand, differences in logP do not notably affect the K-i values for the above receptors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.12.006
• 作为产物：
  描述：

  聚合甲醛 、 四氢-1H-吡咯并[1,2-c]咪唑-1,3(2H)-二酮 、 1-(2-甲氧苯基)哌嗪 以 乙醇 为溶剂， 以85%的产率得到2-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 1. 2-[[4-(o-Methoxyphenyl)piperazin-1-yl]methyl]-1,3- dioxoperhydroimidazo[1,5-a]pyridine:  A Selective 5-HT_1A Receptor Agonist

  摘要：

  A series of new bicyclohydantoin-arylpiperazines was prepared and evaluated for affinity at 5-HT1A, alpha(1), and D-2 receptors. Most of the compounds showed very low affinity for D-2 receptors, and most of them demonstrated moderate to high affinity for 5-HT1A and alpha(1) receptor binding sites. SAR observations indicated that the length of the alkyl chain between the arylpiperazine and the hydantoin moiety is of great importance for 5-HT1A/alpha(1) affinity and selectivity, n = 1 being the optimal value. Compound 1h, 2-[[4-(o-methoxyphenyl)piperazin-1-yl]methyl]-1,3-dioxoperhydroimidazo[1,5-a]pyridine, bound at 5-HT1A sites with nanomolar affinity (K-i = 31.7 nM) and high selectivity over alpha(1), D-2, and 5-HT2A receptors (K-i > 1000, > 10 000, and > 1000 nM, respectively). Preliminary studies showed that this agent is probably functioning as a partial to full 5-HT1A agonist, and it displayed anxiolytic activity on the social interaction test in mice.

  DOI：

  10.1021/jm960416g