14-methyl-5,7,8,13,13b,14-hexahydroindolo[20,30:3,4]pyrido[2,1-b]quinazolin-3-ol | 1615687-57-4

• 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: 14-methyl-5,7,8,13,13b,14-hexahydroindolo[20,30:3,4]pyrido[2,1-b]quinazolin-3-ol
• 英文别名: 3-hydroxy-5-deoxoevodiamine；21-Methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-17-ol；21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-17-ol
• CAS: 1615687-57-4
• 化学式: C₁₉H₁₉N₃O
• 分子量: 305.379
• InChiKey: JLCQVELPUQUIRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  42.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  14-methyl-5,7,8,13,13b,14-hexahydroindolo[20,30:3,4]pyrido[2,1-b]quinazolin-3-ol 、 异氰酸正丁酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以73%的产率得到14-methyl-5,7,8,13,13b,14-hexahydroindolo[2',3':3,4]pyrido[2,1-b]quinazolin-3-ylbutylcarbamate
  参考文献：
  名称：

  Identification of a neuroprotective and selective butyrylcholinesterase inhibitor derived from the natural alkaloid evodiamine

  摘要：

  Two sets of carbamates based on the natural alkaloid evodiamine were designed, synthesized and evaluated as potential butyrylcholinesterase inhibitors. Although a set of carbamates of 3-hydroxyevodiamine (10a-f) is inactive both at AChE and BChE, carbamates of 5-deoxo-3-hydroxyevodiamine (11a-f) exhibit much better potency with selectivity toward BChE. The heptyl carbamate of 5-deoxo-3-hydroxyevodiamine (11c) shows the best potency with an IC50 value of 77 nM and very good selectivity over AChE. ORAC and cell-based assays indicate 11c owns pronounced antioxidant properties with 1.75 Trolox equivalents and strong neuroprotection even from 1 mu M onwards. These combined activities might enable compound 11c to be a potential candidate for treatment of Alzheimer's disease. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.002
• 作为产物：
  描述：

  6-amino-3-benzyloxy-N-ethoxycarbonylbenzoic acid 在 lithium aluminium tetrahydride 、 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 45.0 ℃ 、101.33 kPa 条件下， 反应 48.17h， 生成 14-methyl-5,7,8,13,13b,14-hexahydroindolo[20,30:3,4]pyrido[2,1-b]quinazolin-3-ol
  参考文献：
  名称：

  Identification of a neuroprotective and selective butyrylcholinesterase inhibitor derived from the natural alkaloid evodiamine

  摘要：

  Two sets of carbamates based on the natural alkaloid evodiamine were designed, synthesized and evaluated as potential butyrylcholinesterase inhibitors. Although a set of carbamates of 3-hydroxyevodiamine (10a-f) is inactive both at AChE and BChE, carbamates of 5-deoxo-3-hydroxyevodiamine (11a-f) exhibit much better potency with selectivity toward BChE. The heptyl carbamate of 5-deoxo-3-hydroxyevodiamine (11c) shows the best potency with an IC50 value of 77 nM and very good selectivity over AChE. ORAC and cell-based assays indicate 11c owns pronounced antioxidant properties with 1.75 Trolox equivalents and strong neuroprotection even from 1 mu M onwards. These combined activities might enable compound 11c to be a potential candidate for treatment of Alzheimer's disease. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.002

文献信息

• Identification of a neuroprotective and selective butyrylcholinesterase inhibitor derived from the natural alkaloid evodiamine
  作者：Guozheng Huang、Beata Kling、Fouad H. Darras、Jörg Heilmann、Michael Decker

  DOI：10.1016/j.ejmech.2014.05.002

  日期：2014.6

  Two sets of carbamates based on the natural alkaloid evodiamine were designed, synthesized and evaluated as potential butyrylcholinesterase inhibitors. Although a set of carbamates of 3-hydroxyevodiamine (10a-f) is inactive both at AChE and BChE, carbamates of 5-deoxo-3-hydroxyevodiamine (11a-f) exhibit much better potency with selectivity toward BChE. The heptyl carbamate of 5-deoxo-3-hydroxyevodiamine (11c) shows the best potency with an IC50 value of 77 nM and very good selectivity over AChE. ORAC and cell-based assays indicate 11c owns pronounced antioxidant properties with 1.75 Trolox equivalents and strong neuroprotection even from 1 mu M onwards. These combined activities might enable compound 11c to be a potential candidate for treatment of Alzheimer's disease. (C) 2014 Elsevier Masson SAS. All rights reserved.