(S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]piperazin-2-yl}ethanol | 1584725-38-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]piperazin-2-yl}ethanol
• 英文别名: 2-[(2S)-4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]piperazin-2-yl]ethanol
• CAS: 1584725-38-1
• 化学式: C₂₅H₃₆N₂O₂
• 分子量: 396.573
• InChiKey: BWAGGKXKIPXTBJ-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  35.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-甲氧基-2-萘甲醛 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 sodium sulfate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 51.42h， 生成 (S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]piperazin-2-yl}ethanol
  参考文献：
  名称：

  Synthesis, Pharmacological Evaluation, and σ₁ Receptor Interaction Analysis of Hydroxyethyl Substituted Piperazines

  摘要：

  Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. sigma receptor affinity was recorded using receptor material from both animal and human origin, sigma(1) affinities determined with guinea pig brain and human RPMI 8226 tumor cell lines differed slightly but showed the same tendency. (S)-2-[4-(Cyclohexylmethyl)-1-(naphthalene-2-ylmethyl)piperazin-2-yliethanol (7c) revealed the highest affinity at human sigma(1) receptors (K-i = 6.8 nM). The potent a, receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range. The reduced growth of the RPMI-8226 cell line was caused by apoptosis. The interaction of 7c with the a, receptor was analyzed in detail using the 3D homology model of the sigma(1) receptor. The calculated free binding energies of all hydroxyethylpiperazines nicely correlate with their recorded affinities toward the human a, receptor.

  DOI：

  10.1021/jm401707t

文献信息

• Synthesis, Pharmacological Evaluation, and σ₁ Receptor Interaction Analysis of Hydroxyethyl Substituted Piperazines
  作者：Frauke Weber、Stefanie Brune、Katharina Korpis、Patrick J. Bednarski、Erik Laurini、Valentina Dal Col、Sabrina Pricl、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1021/jm401707t

  日期：2014.4.10

  Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. sigma receptor affinity was recorded using receptor material from both animal and human origin, sigma(1) affinities determined with guinea pig brain and human RPMI 8226 tumor cell lines differed slightly but showed the same tendency. (S)-2-[4-(Cyclohexylmethyl)-1-(naphthalene-2-ylmethyl)piperazin-2-yliethanol (7c) revealed the highest affinity at human sigma(1) receptors (K-i = 6.8 nM). The potent a, receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range. The reduced growth of the RPMI-8226 cell line was caused by apoptosis. The interaction of 7c with the a, receptor was analyzed in detail using the 3D homology model of the sigma(1) receptor. The calculated free binding energies of all hydroxyethylpiperazines nicely correlate with their recorded affinities toward the human a, receptor.