[(3aR,8bS)-3,4-dibenzyl-8b-methyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate | 207729-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [(3aR,8bS)-3,4-dibenzyl-8b-methyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
• CAS: 207729-68-8
• 化学式: C₃₂H₃₁N₃O₂
• 分子量: 489.617
• InChiKey: WWDUYDXEHWHZTJ-BHYZAODMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(3aR,8bS)-3,4-dibenzyl-8b-methyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate 在 palladium dihydroxide 氢气 作用下， 以 异丙醇 为溶剂， 反应 60.0h， 以64.7%的产率得到(-)-N1,N8-bisnorphenylcarbamoyleseroline
  参考文献：
  名称：

  Syntheses and Anticholinesterase Activities of (3aS)-N,N⁸-Bisnorphenserine, (3aS)-N¹,N⁸-Bisnorphysostigmine, Their Antipodal Isomers, and Other Potential Metabolites of Phenserine

  摘要：

  Hydrolysis of the carbamate side chains in phenserine [(-)1] and physostigmine [(-)2] yields the metabolite (-)-eseroline (3), and the red dye rubreserine (4) on air oxidation of the former compound. Both compounds lacked anticholinesterase activity in concentrations up to 30 mM, which would be unachievable in vivo. A second group of potential metabolites of 1 and 2 are the N-1,N-8-bisnorcarbamates (-)9 and (-)10, prepared from (3aS)-N-8-benzylnoresermethole (-)12 by the carbinolamine route. These entirely novel compounds proved to be highly potent inhibitors of acetylcholinesterase [(-)9] and of acetyl- and butyrylcholinesterase (AChE and BChE) [(-)10], respectively. To elucidate further the structure/anticholinesterase activity relationship of the described compounds, the antipodal isomers (3aR)-N-1,N-8-bisnorcarbamates (+)9 and (+)10 were likewise synthesized from (3aR)-N-8-benzylnoresermethole (+)12 and assessed. The compounds possessed moderate but less potent anticholinesterase activity, with the same selectivity as their 3aS enantiomers. Finally, the anticholinesterase activities of intermediates N-1,N-8-bisnorbenzylcarbamates (-)18, (-)19, (+)18, and (+)19, also novel compounds, were additionally measured. The 3aS enantiomers proved to be potent and selective inhibitors of BChE, particularly (-)19, whereas the antipodal isomers lacked activity.

  DOI：

  10.1021/jm9800494
• 作为产物：
  描述：

  (3aS,8aR)-1,2,3,3a,8,8a-Hexahydro-5-methoxy-3a-methyl-1,8-bis(phenylmethyl)pyrrolo[2,3-b]indole 在 sodium 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.1h， 生成 [(3aR,8bS)-3,4-dibenzyl-8b-methyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
  参考文献：
  名称：

  Syntheses and Anticholinesterase Activities of (3aS)-N,N⁸-Bisnorphenserine, (3aS)-N¹,N⁸-Bisnorphysostigmine, Their Antipodal Isomers, and Other Potential Metabolites of Phenserine

  摘要：

  Hydrolysis of the carbamate side chains in phenserine [(-)1] and physostigmine [(-)2] yields the metabolite (-)-eseroline (3), and the red dye rubreserine (4) on air oxidation of the former compound. Both compounds lacked anticholinesterase activity in concentrations up to 30 mM, which would be unachievable in vivo. A second group of potential metabolites of 1 and 2 are the N-1,N-8-bisnorcarbamates (-)9 and (-)10, prepared from (3aS)-N-8-benzylnoresermethole (-)12 by the carbinolamine route. These entirely novel compounds proved to be highly potent inhibitors of acetylcholinesterase [(-)9] and of acetyl- and butyrylcholinesterase (AChE and BChE) [(-)10], respectively. To elucidate further the structure/anticholinesterase activity relationship of the described compounds, the antipodal isomers (3aR)-N-1,N-8-bisnorcarbamates (+)9 and (+)10 were likewise synthesized from (3aR)-N-8-benzylnoresermethole (+)12 and assessed. The compounds possessed moderate but less potent anticholinesterase activity, with the same selectivity as their 3aS enantiomers. Finally, the anticholinesterase activities of intermediates N-1,N-8-bisnorbenzylcarbamates (-)18, (-)19, (+)18, and (+)19, also novel compounds, were additionally measured. The 3aS enantiomers proved to be potent and selective inhibitors of BChE, particularly (-)19, whereas the antipodal isomers lacked activity.

  DOI：

  10.1021/jm9800494

文献信息

• Syntheses and Anticholinesterase Activities of (3a<i>S</i>)-<i>N</i>,<i>N</i>⁸-Bisnorphenserine, (3a<i>S</i>)-<i>N</i>¹,<i>N</i>⁸-Bisnorphysostigmine, Their Antipodal Isomers, and Other Potential Metabolites of Phenserine
  作者：Qian-sheng Yu、Nigel H. Greig、Harold W. Holloway、Arnold Brossi

  DOI：10.1021/jm9800494

  日期：1998.6.1

  Hydrolysis of the carbamate side chains in phenserine [(-)1] and physostigmine [(-)2] yields the metabolite (-)-eseroline (3), and the red dye rubreserine (4) on air oxidation of the former compound. Both compounds lacked anticholinesterase activity in concentrations up to 30 mM, which would be unachievable in vivo. A second group of potential metabolites of 1 and 2 are the N-1,N-8-bisnorcarbamates (-)9 and (-)10, prepared from (3aS)-N-8-benzylnoresermethole (-)12 by the carbinolamine route. These entirely novel compounds proved to be highly potent inhibitors of acetylcholinesterase [(-)9] and of acetyl- and butyrylcholinesterase (AChE and BChE) [(-)10], respectively. To elucidate further the structure/anticholinesterase activity relationship of the described compounds, the antipodal isomers (3aR)-N-1,N-8-bisnorcarbamates (+)9 and (+)10 were likewise synthesized from (3aR)-N-8-benzylnoresermethole (+)12 and assessed. The compounds possessed moderate but less potent anticholinesterase activity, with the same selectivity as their 3aS enantiomers. Finally, the anticholinesterase activities of intermediates N-1,N-8-bisnorbenzylcarbamates (-)18, (-)19, (+)18, and (+)19, also novel compounds, were additionally measured. The 3aS enantiomers proved to be potent and selective inhibitors of BChE, particularly (-)19, whereas the antipodal isomers lacked activity.