4-(4-phenylpiperazin-1-yl)cyclohexan-1-one | 134135-98-1

• 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-(4-phenylpiperazin-1-yl)cyclohexan-1-one
• 英文别名: 4-(1-phenylpiperazin-4-yl)cyclohexanone；4-(4-Phenyl-1-piperazinyl)cyclohexanone
• CAS: 134135-98-1
• 化学式: C₁₆H₂₂N₂O
• mdl: MFCD22682632
• 分子量: 258.363
• InChiKey: HTDYKTPSSROCJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.562
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-phenylpiperazin-1-yl)cyclohexan-1-one 在 ammonium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 4-(1-phenylpiperazin-4-yl)cyclohexylamine
  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：

  N-苯基哌嗪 在 盐酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 42.0h， 生成 4-(4-phenylpiperazin-1-yl)cyclohexan-1-one
  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

• <i>trans</i>-4-[4-(Methoxyphenyl)cyclohexyl]-1-arylpiperazines:  A New Class of Potent and Selective 5-HT_1A Receptor Ligands as Conformationally Constrained Analogues of 4-[3-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1- arylpiperazines
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Marcello Leopoldo、Enza Lacivita、Vincenzo Tortorella、Amedeo Leonardi、Elena Poggesi、Rodolfo Testa

  DOI：10.1021/jm010866v

  日期：2001.12.1

  The present paper concerns the influence of conformational parameters on the recognition by rat 5-HT1A receptors of derivatives 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-(2-pyridinyl)piperazine (1a) and 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-N-[2-(2-pyridyloxy)ethyl]propanamine (3b), two highly potent and selective 5-HT1A receptor ligands. Fifteen corresponding flexible and rigid analogues were prepared following several synthetic routes and were tested in binding assays with radioligands at 5-HT1A, D-2, and alpha (1) receptors from rat brain membranes. Among the new derivatives emerged trans-4-[4-(3-methoxyphenyl)-cyclohexyl]-1-(2-pyridinyl)piperazine (trans-8a) and trans-N-[4-(3-methoxyphenyl)cyclohexyl]-2-(2-pyridyloxy)ethylamine (trans-8b). These compounds can be-considered as conformationally constrained analogues of compounds 1a and 3a, respectively. In fact, compounds trans-8a and trans-8b showed a marked enhancement in 5-HT1A receptor affinity when compared to the corresponding cis isomers. Because compound trans-8a was a potent and selective 5-HT1A ligand (K-i, nM: 5-HT1A = 0.028, D-2 = 2194, alpha (1) = 767), it was chosen as a lead to prepare other analogues that were tested at 5-HT1A, D-2, and alpha (1) receptors from rat brain membranes, showing high affinity at the 5-HT1A and selectivity vs D-2 and alpha (1) receptors. Selected compounds were tested for their affinity at the human cloned 5-HT1A, alpha (1a), alpha (1b), alpha (1d) receptor subtypes. They were also submitted to the [S-35]GTP gammaS binding assay stimulating the 5-HT1A receptor-mediated G-protein activation, therefore behaving as full or as partial agonists. Finally, the ability of iv administration of trans-8a to induce fore-paw treading in rats was evaluated in comparison with 8-OH-DPAT. Although the affinity (K-i) and in vitro activity (pD'(2)) of trans-8a at the 5-HT1A receptor were higher than those of 8-OH-DPAT, the compound was less potent than the reference standard in inducing the symptom.
• US4988699A
  申请人：——

  公开号：US4988699A

  公开（公告）日：1991-01-29
• Aminopyrimidines with High Affinity for Both Serotonin and Dopamine Receptors
  作者：David Wustrow、Thomas Belliotti、Shelly Glase、Suzanne Ross Kesten、Don Johnson、Norman Colbry、Ronald Rubin、Anthony Blackburn、Hyacinth Akunne、Ann Corbin、M. Duff Davis、Lynn Georgic、Steven Whetzel、Kim Zoski、Thomas Heffner、Thomas Pugsley、Lawrence Wise

  DOI：10.1021/jm9707378

  日期：1998.2.1

  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.