N-{[4-(chloromethyl)phenyl]methyl}-5-oxahexacyclo[5.4.1.^02,6.0^3,10.0^4,8.0^9,12]dodecan-4-amine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-{[4-(chloromethyl)phenyl]methyl}-5-oxahexacyclo[5.4.1.^02,6.0^3,10.0^4,8.0^9,12]dodecan-4-amine
• 英文别名: N-[[4-(chloromethyl)phenyl]methyl]-5-oxahexacyclo[5.4.1.02,6.03,10.04,8.09,12]dodecan-4-amine
• 化学式: C₁₉H₂₀ClNO
• 分子量: 313.827
• InChiKey: GUMLISHTDGQOBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-{[4-(chloromethyl)phenyl]methyl}-5-oxahexacyclo[5.4.1.^02,6.0^3,10.0^4,8.0^9,12]dodecan-4-amine 、 炔丙胺 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 20.0~70.0 ℃ 、137.9 kPa 条件下， 反应 2.0h， 以21.57%的产率得到N-[(4-{[(prop-2-yn-1-yl)amino]methyl}phenyl)methyl]-5-oxahexacyclo[5.4.1.0^2,6.0^3,10.0^4,8.0^9,12]dodecan-4-amine
  参考文献：
  名称：

  Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents

  摘要：

  The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The mirr cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 mu M. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 M, when assayed on SHSYSY human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 mu M; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 mu M. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 mu M). Generally, the compounds were about 3-52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.11.051
• 作为产物：
  描述：

  NGP 1-01 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 20.0~70.0 ℃ 、206.0 kPa 条件下， 反应 16.0h， 生成 N-{[4-(chloromethyl)phenyl]methyl}-5-oxahexacyclo[5.4.1.^02,6.0^3,10.0^4,8.0^9,12]dodecan-4-amine
  参考文献：
  名称：

  Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents

  摘要：

  The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The mirr cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 mu M. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 M, when assayed on SHSYSY human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 mu M; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 mu M. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 mu M). Generally, the compounds were about 3-52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.11.051

文献信息

• Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents
  作者：Frank T. Zindo、Sarel F. Malan、Sylvester I. Omoruyi、Adaze B. Enogieru、Okobi E. Ekpo、Jacques Joubert

  DOI：10.1016/j.ejmech.2018.11.051

  日期：2019.2

  The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The mirr cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 mu M. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 M, when assayed on SHSYSY human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 mu M; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 mu M. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 mu M). Generally, the compounds were about 3-52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico. (C) 2018 Elsevier Masson SAS. All rights reserved.