8-benzyl-2-(chloromethyl)-1,4-dioxa-8-azaspiro[4.5]decane

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 8-benzyl-2-(chloromethyl)-1,4-dioxa-8-azaspiro[4.5]decane
• 英文别名: 8-Benzyl-3-(chloromethyl)-1,4-dioxa-8-azaspiro[4.5]decane；8-benzyl-3-(chloromethyl)-1,4-dioxa-8-azaspiro[4.5]decane
• 化学式: C₁₅H₂₀ClNO₂
• 分子量: 281.782
• InChiKey: ZVEQNMZCWONQSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-benzyl-2-(chloromethyl)-1,4-dioxa-8-azaspiro[4.5]decane 在 5%-palladium/activated carbon 、 氢气 、 potassium iodide 作用下， 以 乙醇 、 氯仿 、 乙二醇甲醚 为溶剂， 反应 40.0h， 生成 2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-8-[4-(trifluoromethyl)benzoyl]-1,4-dioxa-8-azaspiro[4.5]decane
  参考文献：
  名称：

  Structure–affinity/activity relationships of 1,4-dioxa-spiro[4.5]decane based ligands at α<alpha>1 and 5-HT1A receptors

  摘要：

  Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a highly selective and potent 5-HT1AR ligand. In the present work we adopted an in-parallel synthetic strategy to rapidly explore a new set of arylpiperazine (7-32) that is structurally related to 1. The compounds were tested for binding affinity and functional activity at 5-HT1AR and alpha < alpha > 1-adrenoceptor subtypes and SAR studies were drawn. In particular, compounds 9, 27 and 30 emerged as promising alpha < alpha > 1 receptor antagonists, while compound 10 behaves as the most potent and efficacious agonist. All the compounds were docked into the 5-HT1AR theoretical model and the results were in agreement with the biological experimental data. These findings may represent a new starting point for developing more selective alpha < alpha > 1 or 5-HT1AR ligands. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.070
• 作为产物：
  描述：

  N-苄基哌啶酮 、 3-氯-1,2-丙二醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 22.0h， 以90%的产率得到8-benzyl-2-(chloromethyl)-1,4-dioxa-8-azaspiro[4.5]decane
  参考文献：
  名称：

  Structure–affinity/activity relationships of 1,4-dioxa-spiro[4.5]decane based ligands at α<alpha>1 and 5-HT1A receptors

  摘要：

  Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a highly selective and potent 5-HT1AR ligand. In the present work we adopted an in-parallel synthetic strategy to rapidly explore a new set of arylpiperazine (7-32) that is structurally related to 1. The compounds were tested for binding affinity and functional activity at 5-HT1AR and alpha < alpha > 1-adrenoceptor subtypes and SAR studies were drawn. In particular, compounds 9, 27 and 30 emerged as promising alpha < alpha > 1 receptor antagonists, while compound 10 behaves as the most potent and efficacious agonist. All the compounds were docked into the 5-HT1AR theoretical model and the results were in agreement with the biological experimental data. These findings may represent a new starting point for developing more selective alpha < alpha > 1 or 5-HT1AR ligands. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.070

文献信息

• Structure-Activity Relationships within a Series of σ₁ and σ₂ Receptor Ligands: Identification of a σ₂ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma
  作者：Silvia Franchini、Claudia Sorbi、Umberto Maria Battisti、Annalisa Tait、Leda Ivanova Bencheva、Elena Cichero、Paola Fossa、Antonio Cilia、Orazio Prezzavento、Simone Ronsisvalle、Giuseppina Aricò、Luisa Benassi、Cristina Vaschieri、Paola Azzoni、Cristina Magnoni、Livio Brasili

  DOI：10.1002/cmdc.201700427

  日期：2017.11.22

  A new series of spirocyclic σ receptor (σR) ligands were prepared and studied. Most were found to have a high affinity and selectivity for σ1R; three compounds were shown to be σ1R agonists, while another proved to be the only σ1R antagonist. Only one of the σ1R agonists (BS148) also exhibited σ2R selectivity and was able to inhibit the growth of metastatic malignant melanoma cell lines without affecting

  制备并研究了一系列新的螺环σ受体（σR）配体。大多数被发现有对σ具有高亲和性和选择性1 R等 三种化合物被证明是σ 1 - [R激动剂，而另一个证明是仅σ 1 - [R拮抗剂。仅之一σ 1 - [R激动剂（BS148）也表现出σ 2 1R选择性，并能够抑制转移性恶性黑色素瘤细胞系的生长，而不影响正常人黑素细胞。该化合物的抗增殖活性建议了一种σ 2 R激动剂曲线。此外，初步研究表明，由BS148诱导的转移性恶性黑色素瘤细胞死亡的机制至少部分是由于细胞凋亡。