(-)-(3aS)-1,3a,8-trimethyl-6-(dimethylamino)methylene-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol | 382637-40-3

• 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: (-)-(3aS)-1,3a,8-trimethyl-6-(dimethylamino)methylene-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol
• CAS: 382637-40-3
• 化学式: C₁₆H₂₅N₃O
• 分子量: 275.394
• InChiKey: FRTHYDSQQLIGPA-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.95
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (-)-(3aS)-1,3a,8-trimethyl-6-(dimethylamino)methylene-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol 在 palladium dihydroxide 氢气 、 sodium 作用下， 以 甲醇 、 乙醚 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.08h， 生成 6-Methylphenserine
  参考文献：
  名称：

  Methyl Analogues of the Experimental Alzheimer Drug Phenserine:  Synthesis and Structure/Activity Relationships for Acetyl- and Butyrylcholinesterase Inhibitory Action

  摘要：

  With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.

  DOI：

  10.1021/jm010080x
• 作为产物：
  描述：

  聚合甲醛 、 盐酸二甲胺 、 氧化毒扁豆碱 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以89%的产率得到(-)-(3aS)-1,3a,8-trimethyl-6-(dimethylamino)methylene-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol
  参考文献：
  名称：

  Methyl Analogues of the Experimental Alzheimer Drug Phenserine:  Synthesis and Structure/Activity Relationships for Acetyl- and Butyrylcholinesterase Inhibitory Action

  摘要：

  With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.

  DOI：

  10.1021/jm010080x