(-)-(3aS)-1,3a,6,8-tetramethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol | 382637-41-4

• 英文名称: (-)-(3aS)-1,3a,6,8-tetramethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol
• 英文别名: (3AS-cis)-1,2,3,3a,8,8a-hexahydro-1,3a,6,8-tetramethylpyrrolo[2,3-b]indol-5-ol；(3aR,8bS)-3,4,6,8b-tetramethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-ol
• CAS: 382637-41-4
• 化学式: C₁₄H₂₀N₂O
• 分子量: 232.326
• InChiKey: ORZDEEKGXMBSSV-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异氰酸甲酯 、 (-)-(3aS)-1,3a,6,8-tetramethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol 在 sodium 作用下， 以 乙醚 为溶剂， 以83%的产率得到6-Methylphysostigmine
  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：

  氧化毒扁豆碱 在 palladium dihydroxide 盐酸 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 (-)-(3aS)-1,3a,6,8-tetramethyl-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

文献信息

• Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents
  申请人：CoLucid Pharmaceuticals, Inc.

  公开号：EP2314571A2

  公开（公告）日：2011-04-27

  Carbamoyl esters inhibit cholinesterase activity and upon hydrolysis release a pharmacologically active agent. The carbamoyl esters are employed in methods to treat an individual. The pharmacologically active agent obtained by hydrolysis of the carbamoyl treat for example,a nervous system condition, cholinergie deficiency and conditions or diseases associated with a deficiency in a pharmacologically active agent such as acetylcholine.

  氨基甲酰基酯可抑制胆碱酯酶的活性，并在水解后释放出具有药理活性的药剂。氨基甲酰基酯可用于治疗疾病。通过水解氨基甲酰基获得的药理活性剂可治疗神经系统疾病、胆碱酯酶缺乏症以及与乙酰胆碱等药理活性剂缺乏有关的疾病。
• US5187165A
  申请人：——

  公开号：US5187165A

  公开（公告）日：1993-02-16