(-)-N8-norphenylcarbamoyleseroline

• 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: (-)-N8-norphenylcarbamoyleseroline
• 英文别名: (�??)-N8-norphenylcarbamoyleseroline；[(3aS,8bS)-3,8b-dimethyl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
• 化学式: C₁₉H₂₁N₃O₂
• 分子量: 323.395
• InChiKey: AGMUUBYEBVEYGU-HKUYNNGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-甲氧基色胺 在 palladium dihydroxide 盐酸 、 sodium hydroxide 、 氢气 、 sodium 、 三溴化硼 、 苄基三甲基溴化铵 、 sodium hydride 、 二甲基亚砜 、 三乙胺 、 红铝 、 三氟乙酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 苯 为溶剂， 反应 16.66h， 生成 (-)-N8-norphenylcarbamoyleseroline
  参考文献：
  名称：

  Total Syntheses and Anticholinesterase Activities of (3aS)-N(8)-Norphysostigmine, (3aS)-N(8)-Norphenserine, Their Antipodal Isomers, and Other N(8)-Substituted Analogues

  摘要：

  N(8)-Benzylesermethole (6) was prepared from 5-methoxytryptamine (1) in five steps. Resolution of compound 6 by dibenzoyl- and ditoluyltartaric acid provided enantiomers (-)- and (+)-7. After demethylation, reaction with isocyanates and catalytic debenzylation over hydrogen, the total syntheses of(-)-and (+)-N(8)-norphysostigmine [(-)-and (+)-11] and (-)-and (+)N(8)-norphenserine [(-)-and (+)-12] were accomplished. (-)-N(8)-Norphysostigmine [(-)-11] and (-)-N(8)-norphenserine [(-)-12] were also obtained by transformations of natural physostigmine [(-)-13] and phenserine [(-)-14] prepared from(-)-13. The absolute configurations and optical purity of compounds (-)-11, (-)-12, (+)-11, and (+)-12 were confirmed by a comparison of their optical rotations with those of the compounds synthesized from physostigmine [(-)-13]. The anticholinesterase activities of N(8)-nor-and N(8)-substituted analogues, (-)-and (+)-9, -10, -11, -12, 15, and 16, were compared with those of physostigmine [(-)-and (+)-13] and phenserine [(-)- and (+)-14] and are reported.

  DOI：

  10.1021/jm970210v

文献信息

• Compositions and methods for inhibiting brain trauma-induced neurodegeneration and related conditions
  申请人：ARISTEA TRANSLATIONAL MEDICINE CORPORATION

  公开号：US10864192B2

  公开（公告）日：2020-12-15

  Compositions and methods for mitigating a pathology following brain trauma or at least a portion of a cascade of a pathology associated therewith, including compositions and methods for treating concussion or preventing the onset of anecrotic cell death in neurons. Exemplary compositions for treating concussion include an active compound comprising one or more of: phenserine, a phenserine metabolite, a phenserine prodrug, or combinations thereof; and one or more pharmaceutically acceptable excipients. The one or more excipients can be combined with the active compound to form an extended, controlled-release medicament that delivers a therapeutic concentration of the active compound over a period of time. Exemplary methods include administering a therapeutic dose of the active compound and, optionally, a therapeutically acceptable dose of a second active compound, and, optionally, maintaining the therapeutic doses of the active and optional second active compounds at therapeutically effective concentrations over a period of time.

  用于减轻脑外伤后的病理变化或与之相关的病理变化级联的至少一部分的组合物和方法，包括用于治疗脑震荡或预防神经元坏死性细胞死亡的组合物和方法。治疗脑震荡的示例性组合物包括一种活性化合物，该化合物包含以下中的一种或多种：表丝氨酸、表丝氨酸代谢物、表丝氨酸原药或其组合；以及一种或多种药学上可接受的赋形剂。一种或多种赋形剂可与活性化合物结合形成缓控释药物，在一段时间内提供治疗浓度的活性化合物。示例性方法包括给药治疗剂量的活性化合物和可选的治疗上可接受剂量的第二活性化合物，以及可选的在一段时间内将治疗剂量的活性化合物和可选的第二活性化合物维持在治疗上有效的浓度。
• 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.
• Total Syntheses and Anticholinesterase Activities of (3a<i>S</i>)-<i>N</i>(8)-Norphysostigmine, (3a<i>S</i>)-<i>N</i>(8)-Norphenserine, Their Antipodal Isomers, and Other <i>N</i>(8)-Substituted Analogues
  作者：Qian-sheng Yu、Xue-Feng Pei、Harold W. Holloway、Nigel H. Greig、Arnold Brossi

  DOI：10.1021/jm970210v

  日期：1997.8.1

  N(8)-Benzylesermethole (6) was prepared from 5-methoxytryptamine (1) in five steps. Resolution of compound 6 by dibenzoyl- and ditoluyltartaric acid provided enantiomers (-)- and (+)-7. After demethylation, reaction with isocyanates and catalytic debenzylation over hydrogen, the total syntheses of(-)-and (+)-N(8)-norphysostigmine [(-)-and (+)-11] and (-)-and (+)N(8)-norphenserine [(-)-and (+)-12] were accomplished. (-)-N(8)-Norphysostigmine [(-)-11] and (-)-N(8)-norphenserine [(-)-12] were also obtained by transformations of natural physostigmine [(-)-13] and phenserine [(-)-14] prepared from(-)-13. The absolute configurations and optical purity of compounds (-)-11, (-)-12, (+)-11, and (+)-12 were confirmed by a comparison of their optical rotations with those of the compounds synthesized from physostigmine [(-)-13]. The anticholinesterase activities of N(8)-nor-and N(8)-substituted analogues, (-)-and (+)-9, -10, -11, -12, 15, and 16, were compared with those of physostigmine [(-)-and (+)-13] and phenserine [(-)- and (+)-14] and are reported.