8-(2,6-dimethylphenyl)-1,4-dioxaspiro[4,5]decane | 1081110-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-(2,6-dimethylphenyl)-1,4-dioxaspiro[4,5]decane
• 英文别名: 8-(2,6-Dimethylphenyl)-1,4-dioxaspiro[4.5]decane
• CAS: 1081110-86-2
• 化学式: C₁₆H₂₂O₂
• 分子量: 246.349
• InChiKey: AMZXGSMAESJQNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-(2,6-dimethylphenyl)-1,4-dioxaspiro[4,5]decane 在 盐酸 、 水 作用下， 以 丙酮 为溶剂， 反应 5.0h， 以80%的产率得到4-(2,6-dimethylphenyl)cyclohexan-1-one
  参考文献：
  名称：

  Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ₈−Δ₇ Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity

  摘要：

  To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some a receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH3, CH3O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 and cis-33 as new ligands with nanomolar affinity toward EBP site and a good selectivity relative to EBP-related a receptors. The most selective 2,6-dimethoxy derivative (cis-33) demonstrated the highest potency (EC50 = 12.9 mu M) and efficacy (70%) in inhibiting proliferation of human prostate cancer PC-3 cell line. Among the reference compounds, sigma(2) agonist 36 (PB28) reached the maximum efficacy (100%), suggesting the contribution of the sigma(2) receptor to the antiproliferative activity, This novel class of EBP inhibitors represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well its a starting point for developing new anticancer drugs.

  DOI：

  10.1021/jm800965b
• 作为产物：
  描述：

  2,6-二甲基溴苯 、 8-溴-1,4-二噁螺[4,5]癸烷 在 magnesium 、 iron(III) chloride 、 四甲基乙二胺 作用下， 以 四氢呋喃 为溶剂， 以1%的产率得到8-(2,6-dimethylphenyl)-1,4-dioxaspiro[4,5]decane
  参考文献：
  名称：

  Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ₈−Δ₇ Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity

  摘要：

  To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some a receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH3, CH3O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 and cis-33 as new ligands with nanomolar affinity toward EBP site and a good selectivity relative to EBP-related a receptors. The most selective 2,6-dimethoxy derivative (cis-33) demonstrated the highest potency (EC50 = 12.9 mu M) and efficacy (70%) in inhibiting proliferation of human prostate cancer PC-3 cell line. Among the reference compounds, sigma(2) agonist 36 (PB28) reached the maximum efficacy (100%), suggesting the contribution of the sigma(2) receptor to the antiproliferative activity, This novel class of EBP inhibitors represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well its a starting point for developing new anticancer drugs.

  DOI：

  10.1021/jm800965b

文献信息

• Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ₈−Δ₇ Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity
  作者：Francesco Berardi、Carmen Abate、Savina Ferorelli、Anna F. de Robertis、Marcello Leopoldo、Nicola A. Colabufo、Mauro Niso、Roberto Perrone

  DOI：10.1021/jm800965b

  日期：2008.12.11

  To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some a receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH3, CH3O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 and cis-33 as new ligands with nanomolar affinity toward EBP site and a good selectivity relative to EBP-related a receptors. The most selective 2,6-dimethoxy derivative (cis-33) demonstrated the highest potency (EC50 = 12.9 mu M) and efficacy (70%) in inhibiting proliferation of human prostate cancer PC-3 cell line. Among the reference compounds, sigma(2) agonist 36 (PB28) reached the maximum efficacy (100%), suggesting the contribution of the sigma(2) receptor to the antiproliferative activity, This novel class of EBP inhibitors represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well its a starting point for developing new anticancer drugs.