3-(2-Adamantyl)-1-(2-diethylaminoethyl)pyrrolidin-2-one | 372945-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-(2-Adamantyl)-1-(2-diethylaminoethyl)pyrrolidin-2-one
• 英文别名: 3-(2-adamantyl)-1-[2-(diethylamino)ethyl]pyrrolidin-2-one
• CAS: 372945-60-3
• 化学式: C₂₀H₃₄N₂O
• 分子量: 318.503
• InChiKey: FHEFKUSEFHZPGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2-Adamantyl)-1-(2-diethylaminoethyl)pyrrolidin-2-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 25.0h， 以80%的产率得到2-[3-(2-adamantyl)pyrrolidin-1-yl]-N,N-diethyl-ethanamine
  参考文献：
  名称：

  Synthesis, conformational characteristics and anti-influenza virus A activity of some 2-adamantylsubstituted azacycles

  摘要：

  The broad-spectrum antiviral activity of 2-(2-adamantyl)piperidines 11, 13a,b, and 15, 3-(2-adamantyl)pyrrolidines 27, 21a-g and 2-(2-adamantylmethyl)piperidines 30, 32a-c, and 35a-d was examined. Several compounds in the new series were potent against influenza A H3N2 virus. When 1-aminoethyl pharmacophore group of 2-rimantadine 4 (2-isomer of rimantadine) is included into a saturated nitrogen heterocycle, see compound 11, potency was retained. The diamine derivatives 21e-g and particularly 35a-c possessing three pharmocophoric groups, that is, the adamantyl and the two amine groups, exhibited high potency. The new compounds did not afford specific activity at non-toxic concentrations against any of the other viruses tested. According to NMR spectroscopy and molecular mechanics calculations it is striking that the parent structures 11 and 27 adopt a fixed trans conformation around C2-C2' bond. In the parent amines, which proved to be active compounds, the distance between nitrogen and adamantyl pharmacophoric groups was different; N-C2' distance is 3.7, 3.8 angstrom for 27, 30 and 2.5 angstrom for 11 suggesting that M2 receptor site can accommodate different in size and orientation lipophilic cages. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2006.05.004
• 作为产物：
  描述：

  2-二乙氨基氯乙烷盐酸盐 在 platinum(IV) oxide 氢气 、 sodium hydride 、 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， -80.0~70.0 ℃ 、275.8 kPa 条件下， 反应 6.33h， 生成 3-(2-Adamantyl)-1-(2-diethylaminoethyl)pyrrolidin-2-one
  参考文献：
  名称：

  Synthesis, conformational characteristics and anti-influenza virus A activity of some 2-adamantylsubstituted azacycles

  摘要：

  The broad-spectrum antiviral activity of 2-(2-adamantyl)piperidines 11, 13a,b, and 15, 3-(2-adamantyl)pyrrolidines 27, 21a-g and 2-(2-adamantylmethyl)piperidines 30, 32a-c, and 35a-d was examined. Several compounds in the new series were potent against influenza A H3N2 virus. When 1-aminoethyl pharmacophore group of 2-rimantadine 4 (2-isomer of rimantadine) is included into a saturated nitrogen heterocycle, see compound 11, potency was retained. The diamine derivatives 21e-g and particularly 35a-c possessing three pharmocophoric groups, that is, the adamantyl and the two amine groups, exhibited high potency. The new compounds did not afford specific activity at non-toxic concentrations against any of the other viruses tested. According to NMR spectroscopy and molecular mechanics calculations it is striking that the parent structures 11 and 27 adopt a fixed trans conformation around C2-C2' bond. In the parent amines, which proved to be active compounds, the distance between nitrogen and adamantyl pharmacophoric groups was different; N-C2' distance is 3.7, 3.8 angstrom for 27, 30 and 2.5 angstrom for 11 suggesting that M2 receptor site can accommodate different in size and orientation lipophilic cages. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2006.05.004

文献信息

• Novel 3-(2-Adamantyl)pyrrolidines with potent activity against influenza A virus—identification of aminoadamantane derivatives bearing two pharmacophoric amine groups
  作者：George Stamatiou、Antonios Kolocouris、Nicolas Kolocouris、George Fytas、George B Foscolos、Johan Neyts、Erik De Clercq

  DOI：10.1016/s0960-894x(01)00388-2

  日期：2001.8

  The 3-(2-adamantyl)pyrrolidines 8a-g. 14 were synthesized and evaluated for activity against influenza A virus. The parent N-H compound 14 was several times more active than amantadine against H2N2 and H3N2 influenza A virus. The combined use of NMR spectroscopy and computational chemistry showed that the conformation around the pyrrolidine-adamantyl carbon-carbon bond is trans and the pyrrolidine heterocycle has an envelope conformation with C-2 out of the plane of the other ring atoms. N-Dialkylaminoethyl substitution of compound 14 resulted in the potent diamine analogues 8e,f,g. Interestingly, their lactam amine precursors were also active. Compounds 8e,f,g are the first adamantane derivatives, bearing two amine groups, reported to be active against influenza A virus. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Synthesis, conformational characteristics and anti-influenza virus A activity of some 2-adamantylsubstituted azacycles
  作者：Despina Setaki、Dimitris Tataridis、George Stamatiou、Antonios Kolocouris、George B. Foscolos、George Fytas、Nicolas Kolocouris、Elizaveta Padalko、Johan Neyts、Erik De Clercq

  DOI：10.1016/j.bioorg.2006.05.004

  日期：2006.10

  The broad-spectrum antiviral activity of 2-(2-adamantyl)piperidines 11, 13a,b, and 15, 3-(2-adamantyl)pyrrolidines 27, 21a-g and 2-(2-adamantylmethyl)piperidines 30, 32a-c, and 35a-d was examined. Several compounds in the new series were potent against influenza A H3N2 virus. When 1-aminoethyl pharmacophore group of 2-rimantadine 4 (2-isomer of rimantadine) is included into a saturated nitrogen heterocycle, see compound 11, potency was retained. The diamine derivatives 21e-g and particularly 35a-c possessing three pharmocophoric groups, that is, the adamantyl and the two amine groups, exhibited high potency. The new compounds did not afford specific activity at non-toxic concentrations against any of the other viruses tested. According to NMR spectroscopy and molecular mechanics calculations it is striking that the parent structures 11 and 27 adopt a fixed trans conformation around C2-C2' bond. In the parent amines, which proved to be active compounds, the distance between nitrogen and adamantyl pharmacophoric groups was different; N-C2' distance is 3.7, 3.8 angstrom for 27, 30 and 2.5 angstrom for 11 suggesting that M2 receptor site can accommodate different in size and orientation lipophilic cages. (c) 2006 Elsevier Inc. All rights reserved.