2-[4-[4-(m-nitrophenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole | 188915-12-0

• 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-(m-nitrophenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole
• 英文别名: 2-[4-[4-(3-Nitrophenyl)piperazin-1-yl]butyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
• CAS: 188915-12-0
• 化学式: C₂₀H₂₇N₅O₄
• 分子量: 401.465
• InChiKey: WLWZLRGOFNRNTJ-UHFFFAOYSA-N

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-(m-nitrophenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以93%的产率得到2-[4-[4-(m-aminophenyl)piperazine-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 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 23.0h， 生成 2-[4-[4-(m-nitrophenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole
  参考文献：
  名称：

  Design and synthesis of 2-[4-[4-(m-(ethylsulfonamido)-phenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole (EF-7412) using neural networks. A selective derivative with mixed antagonist properties

  摘要：

  A test series of 32 phenylpiperazines III with affinity for 5-HT1A and alpha(1) receptors was subjected to QSAR analysis using artificial neural networks (ANNs), in order to get insight into the structural requirements that are responsible for 5-HT1A/alpha(1) selectivity. Good models and predictive power were obtained for 5-HT1A and alpha(1) receptors. A comparison of these models gives information for the design of the new ligand EF-7412 (5-HT1A:K-i (nM)= 27; alpha(1):K-i (nM) > 1000). This derivative displayed affinity for dopamine D-2 receptor (K-i=22 nM) and is selective for all other receptor examined (5-HT2A, 5-HT3, 5-HT3, 5-HT4 and Bz). EF-7412 acts an antagonist in vivo in pre- and postsynaptic 5-MT1A receptor sites and as an antagonist in dopamine D-2 receptor. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00254-1

文献信息

• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT_1A/α₁-Adrenergic Receptor Affinity:  Synthesis of a New Derivative with Mixed 5-HT_1A/D₂ Antagonist Properties
  作者：María L. López-Rodríguez、M. José Morcillo、Esther Fernández、Esther Porras、Luis Orensanz、M Eugenia Beneytez、Jorge Manzanares、Jose Angel Fuentes

  DOI：10.1021/jm000929u

  日期：2001.1.1

  In this paper we have designed and synthesized a test series of 32 amide arylpiperazine derivatives VI in order to gain insight into the physicochemical influence of the pharmacophores of 5-HT1A and alpha (1)-adrenergic receptors. The training set was designed applying a fractional factorial design using six physicochemical descriptors. The amide moiety is a bicyclohydantoin or a diketopiperazine (X = -(CH2)(3)-, -(CH2)(4)-; m = 0, 1), the spacer length is 3 or 4 methylene units, which are the optimum values for both receptors, and the aromatic substituent R occupies the ortho- or meta-position and has been selected from a database of 387 substituents using the EDISFAR program. The 5-HT1A and alpha (1)-adrenergic receptor binding affinities of synthesized compounds VI (1-32) have been determined. This data set has been used to derive classical quantitative structure-activity relationships (QSAR) and neural-networks models for both receptors (following paper). A comparison of these models gives information for the design of the new ligand EF-7412 (46) (5-HT1A: K-i = 27 nM; alpha (1): K-i > 1000 nM). This derivative displays affinity for the dopamine D-2 receptor (K-i = 22 nM) and is selective versus all other receptors examined (5-HT2A, 5-HT3, 5-HT4 and Bz; K-i > 1000 nM). EF-7412 (46) acts as an antagonist in vivo in pre- and postsynaptic 5-HT1A receptor sites and; as an antagonist in the dopamine D-2 receptor. Thus, EF-7412 (46) is a derivative with mixed 5-HT1A/D-2 antagonist properties and this derivative could be useful as a pharmacological tool.