3-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-pentane-1,5-dinitrile | 1194372-95-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 3-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-pentane-1,5-dinitrile
• 英文别名: 3-[3-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]pentanedinitrile
• CAS: 1194372-95-6
• 化学式: C₁₉H₂₄N₂O
• 分子量: 296.412
• InChiKey: LNYKROILMGZYAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-pentane-1,5-dinitrile 在 15-冠醚-5 、 水 、 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 40.0h， 以90%的产率得到3-(carbamoylmethyl)-6-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)hexanoic acid
  参考文献：
  名称：

  Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)

  摘要：

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.

  DOI：

  10.1021/jm9007505
• 作为产物：
  描述：

  sodium cyanide 、 2-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1,3-propanediol dimethanesulfonate 在 15-冠醚-5 作用下， 以 乙腈 为溶剂， 以70%的产率得到3-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-pentane-1,5-dinitrile
  参考文献：
  名称：

  Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)

  摘要：

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.

  DOI：

  10.1021/jm9007505

文献信息

• Exploring the Importance of Piperazine N-Atoms for σ₂ Receptor Affinity and Activity in a Series of Analogs of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28)
  作者：Francesco Berardi、Carmen Abate、Savina Ferorelli、Vincenzo Uricchio、Nicola A. Colabufo、Mauro Niso、Roberto Perrone

  DOI：10.1021/jm9007505

  日期：2009.12.10

  sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms wits alternatively replaced by it methine or converted into an amide or ammonium function, with the aim of finding out which of them was essential For sigma(2) receptor affinity and activity. Some simply 4-substituted 1-cyclohexylpiperazines were also investigated. None of the compounds was as high-affinity as 7 (sigma K-2(i) = 0.68, sigma K-1(i) = 0.38 nM), proving that both basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high-affinity (K-i = 0.11 nM) and noteworthy selective (1627-fold) or, ligand. Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K-i = 4.70 nM). The sigma(2)/sigma(1) selectivities were generally low. Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as putative sigma(2), agonists (EC(50)s 1.40 and 3.64 mu M respectively) more potent than 7.