4-[1-(4-methoxyphenyl)cyclohexen-4-yl]-1-(2-pyridinyl)piperazine | 385811-54-1

• 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-[1-(4-methoxyphenyl)cyclohexen-4-yl]-1-(2-pyridinyl)piperazine
• 英文别名: 1-[4-(4-Methoxyphenyl)cyclohex-3-en-1-yl]-4-pyridin-2-ylpiperazine
• CAS: 385811-54-1
• 化学式: C₂₂H₂₇N₃O
• 分子量: 349.476
• InChiKey: IYBBHHSQYPNOBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  28.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[1-(4-methoxyphenyl)cyclohexen-4-yl]-1-(2-pyridinyl)piperazine 在 10percent Pd/C 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 trans-4-[4-(4-methoxyphenyl)cyclohexyl]-1-(2-pyridinyl)piperazine 、 cis-4-[4-(4-methoxyphenyl)cyclohexyl]-1-(2-pyridinyl)piperazine
  参考文献：
  名称：

  trans-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

  摘要：

  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.

  DOI：

  10.1021/jm010866v
• 作为产物：
  描述：

  4-[4-(2-pyridinyl)piperazin-1-yl]cyclohexan-1-one 在 20percent H₂SO₄ 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 4-[1-(4-methoxyphenyl)cyclohexen-4-yl]-1-(2-pyridinyl)piperazine
  参考文献：
  名称：

  trans-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

  摘要：

  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.

  DOI：

  10.1021/jm010866v

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.