di-tert-butyl N,N'-(4-methyl-4-azaoctane-1,8-diyl)bis[carbamate] | 1032369-44-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: di-tert-butyl N,N'-(4-methyl-4-azaoctane-1,8-diyl)bis[carbamate]
• 英文别名: N-(t-butoxycarbonyl)-N'-[3-(t-butoxycarbonylamino)propyl]-N'-methyl-1,4-butanediamine；tert-butyl N-[3-[methyl-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]amino]propyl]carbamate
• CAS: 1032369-44-0
• 化学式: C₁₈H₃₇N₃O₄
• 分子量: 359.509
• InChiKey: MGGALARILDUCKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  di-tert-butyl N,N'-(4-methyl-4-azaoctane-1,8-diyl)bis[carbamate] 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N¹-methylspermidine
  参考文献：
  名称：

  在人胆碱酯酶的活性位点利用蛋白质波动：进一步优化设计策略，以开发出高效的抑制剂。

  摘要：

  蛋白质构象波动对于生物学功能至关重要，尽管蛋白质运动与功能之间的关系尚待充分研究。通过对胆碱酯酶（ChEs）的全面生物信息学分析，我们确定了引起蛋白质波动和功能的特定热点，以及在关键子结构之间调节合作网络的活性位点残基。这吸引了我们设计策略的优化，以发现有效和可逆的人类乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂（hAChE和hBuChE），这些抑制剂可选择性地与特定蛋白质亚结构相互作用。因此，研究了两个功能不同的连接基间隔不同的三环部分作为分子尺度，以探讨与hChE峡谷中特定热点的最佳相互作用。确定了许多SAR趋势，发现多位点抑制剂3a和3d是迄今为止已知的最有效的hBuChE和hAChE抑制剂。

  DOI：

  10.1021/jm701253t
• 作为产物：
  描述：

  N-Boc-咪唑 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 28.0h， 生成 di-tert-butyl N,N'-(4-methyl-4-azaoctane-1,8-diyl)bis[carbamate]
  参考文献：
  名称：

  Probing the mid-gorge of cholinesterases with spacer-modified bivalent quinazolinimines leads to highly potent and selective butyrylcholinesterase inhibitors

  摘要：

  The spacer structure of homobivalent quinazolinimes acting as potent acetyl-(AChE)- and butyrylcholinesterase (BChE) inhibitors was chemically modified introducing tertiary amine and acyl-amide moieties, and the activities at both ChEs were evaluated. Molecular docking was applied to explain the data and probe the capacity of the mid-gorge site of both ChEs. The novel spacer structures considerably alter the biological profile of bivalent quinazolinimines with regard to both inhibitory activity and selectivity. Mutual interaction of binding to the various sites of the enzymes was further investigated by applying also different spacer lengths and ring sizes of the alicycle of the tricyclic quinazolinimines. In order to achieve selectivity toward BChE and to improve inhibitory activities, the spacer structure was optimized and identified a highly potent and selective BChE inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.034

文献信息

• Development of a new linker for the solid-phase synthesis of N-hydroxylated and N-methylated secondary amines
  作者：Denise Pauli、Stefan Bienz

  DOI：10.1016/j.tet.2013.12.014

  日期：2014.2

  linker moiety to attach amines to the resin by reductive amination. Resin-bound tertiary amines were shown to be readily transferred into the respective liberated N-hydroxylated or N-methylated derivatives by either an oxidation/Cope elimination or a permethylation/Hofmann elimination protocol. With these two divergent liberation/derivatization options, the new resin offers new flexibility in the solid

  Merrifield树脂通过引入邻-硝基苯基乙醛基进行改性，该基用作连接基团以通过还原胺化将胺连接到树脂上。结合树脂的叔胺显示出通过氧化/ Cope消除或全甲基化/霍夫曼消除方案可容易地转移到各自释放的N-羟基化或N-甲基化衍生物中。通过这两种不同的释放/衍生化选项，新树脂在固相合成N-改性仲胺（例如蜘蛛毒素）中提供了新的灵活性。
• Probing the mid-gorge of cholinesterases with spacer-modified bivalent quinazolinimines leads to highly potent and selective butyrylcholinesterase inhibitors
  作者：Xinyu Chen、Irina G. Tikhonova、Michael Decker

  DOI：10.1016/j.bmc.2010.12.034

  日期：2011.2

  The spacer structure of homobivalent quinazolinimes acting as potent acetyl-(AChE)- and butyrylcholinesterase (BChE) inhibitors was chemically modified introducing tertiary amine and acyl-amide moieties, and the activities at both ChEs were evaluated. Molecular docking was applied to explain the data and probe the capacity of the mid-gorge site of both ChEs. The novel spacer structures considerably alter the biological profile of bivalent quinazolinimines with regard to both inhibitory activity and selectivity. Mutual interaction of binding to the various sites of the enzymes was further investigated by applying also different spacer lengths and ring sizes of the alicycle of the tricyclic quinazolinimines. In order to achieve selectivity toward BChE and to improve inhibitory activities, the spacer structure was optimized and identified a highly potent and selective BChE inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.
• Exploiting Protein Fluctuations at the Active-Site Gorge of Human Cholinesterases: Further Optimization of the Design Strategy to Develop Extremely Potent Inhibitors
  作者：Stefania Butini、Giuseppe Campiani、Marianna Borriello、Sandra Gemma、Alessandro Panico、Marco Persico、Bruno Catalanotti、Sindu Ros、Margherita Brindisi、Marianna Agnusdei、Isabella Fiorini、Vito Nacci、Ettore Novellino、Tatyana Belinskaya、Ashima Saxena、Caterina Fattorusso

  DOI：10.1021/jm701253t

  日期：2008.6.1

  network among the key substructures. This drew the optimization of our design strategy to discover potent and reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase (hAChE and hBuChE) that selectively interact with specific protein substructures. Accordingly, two tricyclic moieties differently spaced by functionalized linkers were investigated as molecular yardsticks to probe the

  蛋白质构象波动对于生物学功能至关重要，尽管蛋白质运动与功能之间的关系尚待充分研究。通过对胆碱酯酶（ChEs）的全面生物信息学分析，我们确定了引起蛋白质波动和功能的特定热点，以及在关键子结构之间调节合作网络的活性位点残基。这吸引了我们设计策略的优化，以发现有效和可逆的人类乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂（hAChE和hBuChE），这些抑制剂可选择性地与特定蛋白质亚结构相互作用。因此，研究了两个功能不同的连接基间隔不同的三环部分作为分子尺度，以探讨与hChE峡谷中特定热点的最佳相互作用。确定了许多SAR趋势，发现多位点抑制剂3a和3d是迄今为止已知的最有效的hBuChE和hAChE抑制剂。