4-[2.2]paracyclophanylpiperazine | 511254-86-7

• 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: 4-[2.2]paracyclophanylpiperazine
• 英文别名: ([2.2]paracyclophan-4-yl)piperazine；N-[2.2]paracyclophan-4-ylpiperazine；paracyclophanyl piperazine
• CAS: 511254-86-7
• 化学式: C₂₀H₂₄N₂
• 分子量: 292.424
• InChiKey: SDXNYIZPCMLOGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  15.27
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-[2.2]paracyclophanylpiperazine 、 4-溴丁腈 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以84%的产率得到4-[4-([2.2]paracyclophan-4-yl)piperazin-1-yl]butyronitrile
  参考文献：
  名称：

  Bioisosteric Replacement Leading to Biologically Active [2.2]Paracyclophanes with Altered Binding Profiles for Aminergic G-Protein-Coupled Receptors

  摘要：

  Exploring the chemical diversity space of GPCR ligands, we recently discovered [2.2]paracyclophanes as valuable atypical bioisosteres for secondary affinity and selectivity generating moieties. In find out if such an exchange also works for structural moieties that simulate the endogenous neurotransmitter, pi 1 or pi 2 or both systems pi 1 and pi 2 of three representative privileged structures of types 1, 2. and 3 were replaced by a [2.2]paracyclophane unit. Contributions of the respective functionalities to the binding at of a panel of relevant monoaminergic GPCRs were systematically examined. The study led to the paracyclophanylpiperazine 3a displaying excellent D-3 affinity (K-i = 1.6 nM) and a strongly attenuated binding to D-4, 5-HT1 and alpha(1). Whereas functional experiments showed neutral D-3 antagonist properties, mutagenesis studies indicated a binding mode that is similar to its lead compounds of type 3.

  DOI：

  10.1021/jm100899z
• 作为产物：
  描述：

  4-溴[2.2]对环芳烷 在 盐酸 、 potassium tert-butylate 作用下， 以 甲苯 为溶剂， 反应 43.0h， 生成 4-[2.2]paracyclophanylpiperazine
  参考文献：
  名称：

  Analogs of the dopamine D4 receptor ligand FAUC 113 with planar- and central-chirality

  摘要：

  employing yeast enzymes, natural amino acids and the Jacobsen's catalyst as sources of chirality, we have synthesized pyrazolo[1,5-a]pyridine derivatives with central- and planar-chirality as analogs of the dopamine D4 receptor ligand FAUC 113. In vitro binding experiments displayed enhanced D2 and D3 affinity for both enantiomers of the [2.2]paracyclophane 3. The C-methylpiperazine (R)-4a revealed excellent D4 selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00639-0

文献信息

• Discovery of dopamine D4 receptor antagonists with planar chirality
  作者：Fabrizio Sanna、Birgit Ortner、Harald Hübner、Stefan Löber、Nuska Tschammer、Peter Gmeiner

  DOI：10.1016/j.bmc.2013.01.065

  日期：2013.4

  Employing the D-4 selective phenylpiperazine 2 as a lead compound, planar chiral analogs with paracyclophane substructure were synthesized and evaluated for their ability to bind and activate dopamine receptors. The study revealed that the introduction of a [2.2]paracyclophane moiety is tolerated by dopamine receptors of the D-2 family. Subtype selectivity for D-4 and ligand efficacy depend on the absolute configuration of the test compounds. Whereas the achiral single-layered lead 2 and the double-layered paracyclophane (R)-3 showed partial agonist properties, the enantiomer (S)-3 behaved as a neutral antagonist. (C) 2013 Elsevier Ltd. All rights reserved.