4-[2-(4-phenylpiperazin-1-yl)ethyl]cyclohexan-1-amine | 189153-13-7

• 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-(4-phenylpiperazin-1-yl)ethyl]cyclohexan-1-amine
• CAS: 189153-13-7
• 化学式: C₁₈H₂₉N₃
• 分子量: 287.448
• InChiKey: PTJVENXUBXYLGL-UHFFFAOYSA-N

物化性质

• 沸点：
  421.5±30.0 °C(Predicted)
• 密度：
  1.025±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(4-phenylpiperazin-1-yl)ethyl]cyclohexan-1-amine 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 112.0h， 生成
  参考文献：
  名称：

  Aminopyrimidines with High Affinity for Both Serotonin and Dopamine Receptors

  摘要：

  A series of {4-[2-(4-arylpiperazin-1-yl)alkyl]cyclohexyl}pyrimidin-2-ylamines was prepared and found to have receptor binding affinity for D2 and D3 dopamine (DA) receptors and serotonin 5-HT1A receptors. The structural contributions to D2/D3 and 5-HT1A receptor binding of the aminopyrimidine, cycloalkyl, and phenylpiperazine portions of the molecule were examined. From these studies compounds 14, 39, 42, 43, having potent affinity for both DA D2 and 5-HT1A receptors, were evaluated for intrinsic activity at these receptors, in vitro and in vivo. Compound 14 (PD 158771) had a profile indicative of partial agonist activity at both D2 and 5-HT1A receptors causing partially decreased synthesis of the neurotransmitters DA and 5-HT and their metabolites. This compound has a profile in behavioral tests that is predictive of antipsychotic activity, suggesting that mixed, partial agonists such as 14 may have utility as antipsychotic agents with increased efficacy and decreased side effects.

  DOI：

  10.1021/jm9707378
• 作为产物：
  描述：

  2-(1,4-dioxaspiro[4,5]dec-8-yl)-1-(4-phenyl-1-piperazinyl)ethanone 在 盐酸 、 lithium aluminium tetrahydride 、 三氯化铝 、 ammonium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙醚 、 丙酮 为溶剂， 反应 96.0h， 生成 4-[2-(4-phenylpiperazin-1-yl)ethyl]cyclohexan-1-amine
  参考文献：
  名称：

  Aminopyrimidines with High Affinity for Both Serotonin and Dopamine Receptors

  摘要：

  A series of {4-[2-(4-arylpiperazin-1-yl)alkyl]cyclohexyl}pyrimidin-2-ylamines was prepared and found to have receptor binding affinity for D2 and D3 dopamine (DA) receptors and serotonin 5-HT1A receptors. The structural contributions to D2/D3 and 5-HT1A receptor binding of the aminopyrimidine, cycloalkyl, and phenylpiperazine portions of the molecule were examined. From these studies compounds 14, 39, 42, 43, having potent affinity for both DA D2 and 5-HT1A receptors, were evaluated for intrinsic activity at these receptors, in vitro and in vivo. Compound 14 (PD 158771) had a profile indicative of partial agonist activity at both D2 and 5-HT1A receptors causing partially decreased synthesis of the neurotransmitters DA and 5-HT and their metabolites. This compound has a profile in behavioral tests that is predictive of antipsychotic activity, suggesting that mixed, partial agonists such as 14 may have utility as antipsychotic agents with increased efficacy and decreased side effects.

  DOI：

  10.1021/jm9707378

文献信息

• CARBONYLATED (AZA) CYCLOHEXANES AS DOPAMINE D3 RECEPTOR LIGANDS
  申请人：Capet Marc

  公开号：US20090286801A1

  公开（公告）日：2009-11-19

  The invention relates to compounds of the general formula (I): to the process for preparing them, and to the use thereof as a therapeutic agent.

  该发明涉及通式(I)的化合物，其制备过程以及作为治疗剂的用途。
• Substituted cyclohexylamines as central nervous systems agents
  申请人：Warner-Lambert Company

  公开号：US05977110A1

  公开（公告）日：1999-11-02

  Substituted cyclohexylamines and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful as central nervous system agents and are particularly useful as dopaminergic, serotonergic, antipsychotic, and anxiolytic agents.

  本文描述了取代的环己胺及其衍生物，以及制备方法和制药组合物，其作为中枢神经系统药物非常有用，特别是作为多巴胺能、血清素能、抗精神病和抗焦虑药物。
• Carbonylated (Aza)cyclohexanes as dopamine D3 receptor ligands
  申请人：BIOPROJET

  公开号：EP1870405A1

  公开（公告）日：2007-12-26

  The invention relates to compounds of the general formula (I): to the process for preparing them, and to the use thereof as a therapeutic agent.

  本发明涉及通式 (I) 的化合物： 以及将其用作治疗剂的方法。
• Novel cyclohexyl amides as potent and selective D3 dopamine receptor ligands
  作者：Thomas R. Belliotti、Suzanne R. Kesten、John R. Rubin、David J. Wustrow、Lynn M. Georgic、Kim T. Zoski、Hyacinth C. Akunne、Lawrence D. Wise

  DOI：10.1016/s0960-894x(97)00443-5

  日期：1997.9

  The dopamine D-3 receptor is an attractive target for the treatment of schizophrenia. We identified PD137557 (V) as a ligand for the D-2 receptor and desired to prepare a selective D3 compound. SAR studies involving different amides and different phenyl piperazines have led to the discovery of 8a and 8c as selective D-3 receptor ligands. (C) 1997 Elsevier Science Ltd.
• Discovery of cariprazine (RGH-188): A novel antipsychotic acting on dopamine D3/D2 receptors
  作者：Éva Ágai-Csongor、György Domány、Katalin Nógrádi、János Galambos、István Vágó、György Miklós Keserű、István Greiner、István Laszlovszky、Anikó Gere、Éva Schmidt、Béla Kiss、Mónika Vastag、Károly Tihanyi、Katalin Sághy、Judit Laszy、István Gyertyán、Mária Zájer-Balázs、Larisza Gémesi、Margit Kapás、Zsolt Szombathelyi

  DOI：10.1016/j.bmcl.2012.03.104

  日期：2012.5

  Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D-3/D-2 compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D-3 and D-2 receptors. Several members of this group showed excellent pharmacokinetic and pharmacodynamic properties as demonstrated by outstanding activities in different antipsychotic tests. The most promising representative, 2m (cariprazine) had good absorption, excellent brain penetration and advantageous safety profile. Based on its successful clinical development we are looking forward to the NDA filing of cariprazine in 2012. (C) 2012 Elsevier Ltd. All rights reserved.