(3aR,8aR)-1,8-dimethyl-3a-ethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate | 1396316-87-2

• 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,8aR)-1,8-dimethyl-3a-ethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate
• 英文别名: (3aS,8aR)-1,8-dimethyl-3a-ethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate；[(3aR,8bS)-8b-ethyl-3,4-dimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
• CAS: 1396316-87-2
• 化学式: C₂₁H₂₅N₃O₂
• 分子量: 351.448
• InChiKey: JRMZFWBHWGXMJV-CTNGQTDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-乙酰基-5-甲氧基-2H-吲哚-3-酮 在 甲醇 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 lithium aluminium tetrahydride 、 lithium hydroxide monohydrate 、 三丁基膦 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 双氧水 、 溴 、 sodium 、 三溴化硼 、 sodium hydride 、 N-甲基吗啉氧化物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 212.0h， 生成 (3aR,8aR)-1,8-dimethyl-3a-ethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate
  参考文献：
  名称：

  Synthesis of phenserine analogues and evaluation of their cholinesterase inhibitory activities

  摘要：

  Phenserine is a potentially attractive drug for Alzheimer's disease. In order to further expand SAR study for inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), the methyl group at the 3a-position of phenserine was replaced with an alkyl or alkenyl group, and its phenylcarbamoyl moiety was substituted at the o- or p-position. The synthetic methodology for these phenserine analogues includes the efficient cascade reactions for introduction of the 3a-substituent and assembly of the quaternary carbon center followed by reductive cyclization to the key pyrroloindoline structure. The bulkiness of the substituent at 3a-position of phenserine derivatives tends to reduce the inhibitory effect on AChE activity in the following order: methyl > ethyl > vinyl > propyl approximate to allyl > reverse-prenyl groups. Among the series synthesized, the 3a-ethyl derivative demonstrated the highest AChE selectivity. In construct, the 3a-reverse-prenyl derivative indicated modest BuChE selectivity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.048

文献信息

• Synthesis of phenserine analogues and evaluation of their cholinesterase inhibitory activities
  作者：Masashi Shinada、Fuminori Narumi、Yuji Osada、Koji Matsumoto、Takayasu Yoshida、Kazuhiro Higuchi、Tomomi Kawasaki、Hiroyuki Tanaka、Mitsutoshi Satoh

  DOI：10.1016/j.bmc.2012.06.048

  日期：2012.8

  Phenserine is a potentially attractive drug for Alzheimer's disease. In order to further expand SAR study for inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), the methyl group at the 3a-position of phenserine was replaced with an alkyl or alkenyl group, and its phenylcarbamoyl moiety was substituted at the o- or p-position. The synthetic methodology for these phenserine analogues includes the efficient cascade reactions for introduction of the 3a-substituent and assembly of the quaternary carbon center followed by reductive cyclization to the key pyrroloindoline structure. The bulkiness of the substituent at 3a-position of phenserine derivatives tends to reduce the inhibitory effect on AChE activity in the following order: methyl > ethyl > vinyl > propyl approximate to allyl > reverse-prenyl groups. Among the series synthesized, the 3a-ethyl derivative demonstrated the highest AChE selectivity. In construct, the 3a-reverse-prenyl derivative indicated modest BuChE selectivity. (C) 2012 Elsevier Ltd. All rights reserved.