tert-butyl-N-(3-{methyl[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]amino}propyl)carbamate | 823190-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl-N-(3-{methyl[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]amino}propyl)carbamate
• 英文别名: tert-butyl N-[3-[methyl-[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]amino]propyl]carbamate
• CAS: 823190-32-5
• 化学式: C₂₅H₃₇N₃O₂S
• 分子量: 443.654
• InChiKey: QGJPHGWWGTZZJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl-N-(3-{methyl[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]amino}propyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N¹-methyl-N¹-[3-(1,2,3,4-tetrahydro-acridin-9-ylsulfanyl)-propyl]-propane-1,3-diamine
  参考文献：
  名称：

  Development of Molecular Probes for the Identification of Extra Interaction Sites in the Mid-Gorge and Peripheral Sites of Butyrylcholinesterase (BuChE). Rational Design of Novel, Selective, and Highly Potent BuChE Inhibitors

  摘要：

  Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge.

  DOI：

  10.1021/jm049510k
• 作为产物：
  描述：

  9-Thio-1,2,3,4-tetrahydroacridanone 在 氢氧化钾 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 tert-butyl-N-(3-{methyl[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]amino}propyl)carbamate
  参考文献：
  名称：

  Development of Molecular Probes for the Identification of Extra Interaction Sites in the Mid-Gorge and Peripheral Sites of Butyrylcholinesterase (BuChE). Rational Design of Novel, Selective, and Highly Potent BuChE Inhibitors

  摘要：

  Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge.

  DOI：

  10.1021/jm049510k

文献信息

• Development of Molecular Probes for the Identification of Extra Interaction Sites in the Mid-Gorge and Peripheral Sites of Butyrylcholinesterase (BuChE). Rational Design of Novel, Selective, and Highly Potent BuChE Inhibitors
  作者：Giuseppe Campiani、Caterina Fattorusso、Stefania Butini、Alessandra Gaeta、Marianna Agnusdei、Sandra Gemma、Marco Persico、Bruno Catalanotti、Luisa Savini、Vito Nacci、Ettore Novellino、Harold W. Holloway、Nigel H. Greig、Tatyana Belinskaya、James M. Fedorko、Ashima Saxena

  DOI：10.1021/jm049510k

  日期：2005.3.1

  Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge.