1-(4-cyclohexylpiperazin-1-yl)-5-[2(1H)-oxo-3,4-dihydro-1,8-naphthyridin-1-yl]pentan-1-one | 1417626-73-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: 1-(4-cyclohexylpiperazin-1-yl)-5-[2(1H)-oxo-3,4-dihydro-1,8-naphthyridin-1-yl]pentan-1-one
• CAS: 1417626-73-3
• 化学式: C₂₃H₃₄N₄O₂
• 分子量: 398.549
• InChiKey: NJQZIRONPIOGTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  56.75
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-(4-cyclohexylpiperazin-1-yl)-5-[2(1H)-oxo-3,4-dihydro-1,8-naphthyridin-1-yl]pentan-1-one 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以90%的产率得到
  参考文献：
  名称：

  2-Aminopyridine Derivatives as Potential σ₂Receptor Antagonists

  摘要：

  Abstractσ2 Receptor research is receiving increasing interest with regard to the potential of σ2 proteins as targets for tumor therapy and diagnosis. Nevertheless, knowledge about the σ2 receptor is far from conclusive. The paucity and modest affinity of known σ2 antagonists represent one of the limitations to σ2 receptor research. Previous studies of the high‐affinity σ2 agonist 1‐cyclohexyl‐4‐[3‐(5‐methoxy‐1,2,3,4‐tetrahydronaphthalen‐1‐yl)‐n‐propyl]piperazine 4 (PB28) suggested that a decrease in lipophilicity might lead to σ2 ligands devoid of antiproliferative activity (potential σ2 antagonists). With the aim of producing σ2 receptor antagonists, we replaced the tetralin nucleus of compound 4 with a 2‐aminopyridine moiety. A series of compounds with high affinity for both σ subtypes and with no antiproliferative activity in various cells (mouse HT‐22, human SK‐N‐SH, MCF‐7wt, and MCF‐7σ1) were obtained. The effect on Ca2+ mobilization was investigated for high‐affinity compounds 18 and 4, which showed opposite effects. All of the data support the new 2‐aminopyridines as high‐affinity σ ligands with σ2 antagonist and σ1 agonist activity, and, despite the lack of significant σ2 versus σ1 selectivity, these novel compounds may be better tools for σ receptor research than the known low‐affinity σ2 antagonists.

  DOI：

  10.1002/cmdc.201200246
• 作为产物：
  描述：

  2-amino-3-(bromomethyl)pyridine hydrobromide 在 sodium methylate 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 71.0h， 生成 1-(4-cyclohexylpiperazin-1-yl)-5-[2(1H)-oxo-3,4-dihydro-1,8-naphthyridin-1-yl]pentan-1-one
  参考文献：
  名称：

  2-Aminopyridine Derivatives as Potential σ₂Receptor Antagonists

  摘要：

  Abstractσ2 Receptor research is receiving increasing interest with regard to the potential of σ2 proteins as targets for tumor therapy and diagnosis. Nevertheless, knowledge about the σ2 receptor is far from conclusive. The paucity and modest affinity of known σ2 antagonists represent one of the limitations to σ2 receptor research. Previous studies of the high‐affinity σ2 agonist 1‐cyclohexyl‐4‐[3‐(5‐methoxy‐1,2,3,4‐tetrahydronaphthalen‐1‐yl)‐n‐propyl]piperazine 4 (PB28) suggested that a decrease in lipophilicity might lead to σ2 ligands devoid of antiproliferative activity (potential σ2 antagonists). With the aim of producing σ2 receptor antagonists, we replaced the tetralin nucleus of compound 4 with a 2‐aminopyridine moiety. A series of compounds with high affinity for both σ subtypes and with no antiproliferative activity in various cells (mouse HT‐22, human SK‐N‐SH, MCF‐7wt, and MCF‐7σ1) were obtained. The effect on Ca2+ mobilization was investigated for high‐affinity compounds 18 and 4, which showed opposite effects. All of the data support the new 2‐aminopyridines as high‐affinity σ ligands with σ2 antagonist and σ1 agonist activity, and, despite the lack of significant σ2 versus σ1 selectivity, these novel compounds may be better tools for σ receptor research than the known low‐affinity σ2 antagonists.

  DOI：

  10.1002/cmdc.201200246