2-{4-[4-(4-Nitro-phenyl)-piperazin-1-yl]-butyl}-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione | 188915-07-3

• 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-[4-(4-Nitro-phenyl)-piperazin-1-yl]-butyl}-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione
• 英文别名: 2-[4-[4-(4-Nitrophenyl)piperazin-1-yl]butyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
• CAS: 188915-07-3
• 化学式: C₂₀H₂₇N₅O₄
• 分子量: 401.465
• InChiKey: DNDDBNQMBXMCHY-UHFFFAOYSA-N

物化性质

• 沸点：
  574.4±60.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  92.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-{4-[4-(4-Nitro-phenyl)-piperazin-1-yl]-butyl}-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以87%的产率得到2-{4-[4-(p-aminophenyl)piperazin-1-yl]butyl}-1,3-dioxoperhydropyrrolo[1,2-c]imidazole
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 2. Three-Dimensional Quantitative Structure−Activity Relationships of Hydantoin−Phenylpiperazine Derivatives with Affinity for 5-HT_1A and α₁ Receptors. A Comparison of CoMFA Models

  摘要：

  A series of 48 bicyclohydantoin-phenylpiperazines (1-4) with affinity for 5-HT1A and alpha(1) receptors was subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis (CoMFA), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha(1) selectivity. Good models (high cross-validation correlations and predictive power) were obtained for 5-HT1A and alpha(1) receptors. The resulting 3D-QSAR models rationalize steric and electrostatic factors which modulate binding to 5-HT1A and alpha(1) receptors. A comparison of these models gives an additional understanding for 5-HT1A/alpha(1) selectivity: (a) Substitution at the ortho position by a group with negative potential is favorable to affinity for both receptors. (b) The meta position seems to be implicated in 5-HT1A/alpha(1) selectivity. While the 5-HT1A receptor is able to accommodate bulky substituents in the region of its active site, the steric requirements of the alpha(1) receptor are more restricted (optimum volume of substituent 11-25 Angstrom(3)). (c) For both receptors the para position represents a region where the volume accessible by the ligands is limited. (d) The hydantoin moiety and the side chain length seem to modulate not only the affinity but also 5-HT1A/alpha(1) selectivity. The 3D-QSAR models reveal an useful predictive information for the design of new selective ligands.

  DOI：

  10.1021/jm960744g
• 作为产物：
  描述：

  四氢-1H-吡咯并[1,2-c]咪唑-1,3(2H)-二酮 在 sodium hydride 、 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 2-{4-[4-(4-Nitro-phenyl)-piperazin-1-yl]-butyl}-tetrahydro-pyrrolo[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

文献信息

• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 1. 2-[[4-(<i>o</i>-Methoxyphenyl)piperazin-1-yl]methyl]-1,3- dioxoperhydroimidazo[1,5-<i>a</i>]pyridine:  A Selective 5-HT_1A Receptor Agonist
  作者：María L. López-Rodríguez、M Luisa Rosado、Bellinda Benhamú、M José Morcillo、Antonio M. Sanz、Luis Orensanz、M Eugenia Beneitez、José A. Fuentes、Jorge Manzanares

  DOI：10.1021/jm960416g

  日期：1996.1.1

  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.
• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 2. Three-Dimensional Quantitative Structure−Activity Relationships of Hydantoin−Phenylpiperazine Derivatives with Affinity for 5-HT_1A and α₁ Receptors. A Comparison of CoMFA Models
  作者：María L. López-Rodríguez、M Luisa Rosado、Bellinda Benhamú、M José Morcillo、Esther Fernández、Klaus-Jürgen Schaper

  DOI：10.1021/jm960744g

  日期：1997.5.1

  A series of 48 bicyclohydantoin-phenylpiperazines (1-4) with affinity for 5-HT1A and alpha(1) receptors was subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis (CoMFA), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha(1) selectivity. Good models (high cross-validation correlations and predictive power) were obtained for 5-HT1A and alpha(1) receptors. The resulting 3D-QSAR models rationalize steric and electrostatic factors which modulate binding to 5-HT1A and alpha(1) receptors. A comparison of these models gives an additional understanding for 5-HT1A/alpha(1) selectivity: (a) Substitution at the ortho position by a group with negative potential is favorable to affinity for both receptors. (b) The meta position seems to be implicated in 5-HT1A/alpha(1) selectivity. While the 5-HT1A receptor is able to accommodate bulky substituents in the region of its active site, the steric requirements of the alpha(1) receptor are more restricted (optimum volume of substituent 11-25 Angstrom(3)). (c) For both receptors the para position represents a region where the volume accessible by the ligands is limited. (d) The hydantoin moiety and the side chain length seem to modulate not only the affinity but also 5-HT1A/alpha(1) selectivity. The 3D-QSAR models reveal an useful predictive information for the design of new selective ligands.