methyl (S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]-3,6-dioxopiperazin-2-yl}acetate | 1584725-61-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl (S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]-3,6-dioxopiperazin-2-yl}acetate
• CAS: 1584725-61-0
• 化学式: C₂₆H₃₂N₂O₅
• 分子量: 452.55
• InChiKey: WJPJUYJBLFBSIX-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.53
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.15
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]-3,6-dioxopiperazin-2-yl}acetate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.17h， 以50%的产率得到(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
• 作为产物：
  描述：

  在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 18.5h， 生成 methyl (S)-2-{4-(cyclohexylmethyl)-1-[(6-methoxynaphthalen-2-yl)methyl]-3,6-dioxopiperazin-2-yl}acetate
  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