N,N'-(dodecane-1,12-diyl)bis(6-aminohexanamide) | 1443761-09-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N,N'-(dodecane-1,12-diyl)bis(6-aminohexanamide)
• 英文别名: 6-amino-N-[12-(6-aminohexanoylamino)dodecyl]hexanamide
• CAS: 1443761-09-8
• 化学式: C₂₄H₅₀N₄O₂
• 分子量: 426.687
• InChiKey: PVYLYKAEFCZKIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  23
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N'-(dodecane-1,12-diyl)bis(6-aminohexanamide) 在 borane N-ethyl-N-isopropylaniline complex 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二乙二醇二甲醚 为溶剂， 反应 5.0h， 生成 N¹,N^1'-(dodecane-1,12-diyl)bis(N⁶-(2,2-diphenylethyl)hexane-1,6-diamine)
  参考文献：
  名称：

  Synthetic polyamines activating autophagy: Effects on cancer cell death

  摘要：

  The ability of symmetrically substituted long chain polymethylene tetramines, methoctramine (1) and its analogs 2-4 to kill cancer cells was studied. We found that an elevated cytotoxicity was correlated with a 12 methylene chain length separating the inner amine functions (6-12-6 carbon backbone), together with the introduction of diphenylethyl moieties on the terminal nitrogen atoms (compound 4) of a tetramine backbone. Compound 4 triggered dissipation of mitochondrial transmembrane potential and increased intracellular peroxide levels, leading to a caspase-independent HeLa cell death associated with a rapid activation of autophagy. The antioxidant N-acetylcysteine inhibited cell death and activation of autophagy, indicating a link between oxidative stress and autophagy. Autophagy was rapidly triggered even by tetramines 2 and 3, indicating that is related to their polyamine structure. Autophagy did not protect HeLa cells against cytotoxicity elicited by compound 4. The present study shows that, by modifications of the methoctramine structure, it is possible to design polyamine derivatives highly cytotoxic against tumor cells and that the appropriate design of molecules bearing polyamine-like structures leads to powerful inducers of autophagy. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.044
• 作为产物：
  描述：

  dibenzyl ((dodecane-1,12-diylbis(azanediyl))bis(6-oxohexane-6,1-diyl))dicarbamate 在 氢溴酸 、 sodium hydroxide 作用下， 以 氯仿 、 溶剂黄146 为溶剂， 反应 18.0h， 生成 N,N'-(dodecane-1,12-diyl)bis(6-aminohexanamide)
  参考文献：
  名称：

  In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers

  摘要：

  The biological activities of six symmetrically substituted 2-methoxy-benzyl polymethylene tetraamines (1-4) and diphenylethyl polymethylene tetraamines (5 and 6) as N-methyl-D-aspartate (NMDA) receptor channel blockers, were evaluated in vitro and in vivo. Although all compounds exhibited stronger channel block activities in comparison to memantine in Xenopus oocytes voltage clamped at -70 mV, only compound 2 (0.4 mg/kg intravenous injection) decreased the size of brain infarction in a photochemically induced thrombosis model mice at the same extent of memantine (10 mg/kg intravenous injection). Other compounds (1, 3, 4, 5 and 6) did not decrease the size of brain infarction significantly due to the limited injection doses. The present study suggests that compound 2 could represent a valuable lead compound to design low toxicity polyamines for clinical use against stroke. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.063

文献信息

• Synthetic polyamines activating autophagy: Effects on cancer cell death
  作者：Anna Minarini、Maddalena Zini、Andrea Milelli、Vincenzo Tumiatti、Chiara Marchetti、Benedetta Nicolini、Mirella Falconi、Giovanna Farruggia、Concettina Cappadone、Claudio Stefanelli

  DOI：10.1016/j.ejmech.2013.06.044

  日期：2013.9

  The ability of symmetrically substituted long chain polymethylene tetramines, methoctramine (1) and its analogs 2-4 to kill cancer cells was studied. We found that an elevated cytotoxicity was correlated with a 12 methylene chain length separating the inner amine functions (6-12-6 carbon backbone), together with the introduction of diphenylethyl moieties on the terminal nitrogen atoms (compound 4) of a tetramine backbone. Compound 4 triggered dissipation of mitochondrial transmembrane potential and increased intracellular peroxide levels, leading to a caspase-independent HeLa cell death associated with a rapid activation of autophagy. The antioxidant N-acetylcysteine inhibited cell death and activation of autophagy, indicating a link between oxidative stress and autophagy. Autophagy was rapidly triggered even by tetramines 2 and 3, indicating that is related to their polyamine structure. Autophagy did not protect HeLa cells against cytotoxicity elicited by compound 4. The present study shows that, by modifications of the methoctramine structure, it is possible to design polyamine derivatives highly cytotoxic against tumor cells and that the appropriate design of molecules bearing polyamine-like structures leads to powerful inducers of autophagy. (C) 2013 Elsevier Masson SAS. All rights reserved.
• In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers
  作者：Ryotaro Saiki、Yuki Yoshizawa、Anna Minarini、Andrea Milelli、Chiara Marchetti、Vincenzo Tumiatti、Toshihiko Toida、Keiko Kashiwagi、Kazuei Igarashi

  DOI：10.1016/j.bmcl.2013.04.063

  日期：2013.7

  The biological activities of six symmetrically substituted 2-methoxy-benzyl polymethylene tetraamines (1-4) and diphenylethyl polymethylene tetraamines (5 and 6) as N-methyl-D-aspartate (NMDA) receptor channel blockers, were evaluated in vitro and in vivo. Although all compounds exhibited stronger channel block activities in comparison to memantine in Xenopus oocytes voltage clamped at -70 mV, only compound 2 (0.4 mg/kg intravenous injection) decreased the size of brain infarction in a photochemically induced thrombosis model mice at the same extent of memantine (10 mg/kg intravenous injection). Other compounds (1, 3, 4, 5 and 6) did not decrease the size of brain infarction significantly due to the limited injection doses. The present study suggests that compound 2 could represent a valuable lead compound to design low toxicity polyamines for clinical use against stroke. (c) 2013 Elsevier Ltd. All rights reserved.