3-(2-chloroacetamino)-7,8-dehydrorutaecarpine | 1202403-70-0

• 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: 3-(2-chloroacetamino)-7,8-dehydrorutaecarpine
• 英文别名: 3-(2-chloroacetamido)-7,8-dehydrorutaecarpine；2-chloro-N-(14-oxo-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-1(21),2(10),4,6,8,11,15(20),16,18-nonaen-17-yl)acetamide
• CAS: 1202403-70-0
• 化学式: C₂₀H₁₃ClN₄O₂
• 分子量: 376.802
• InChiKey: CCEQPVTWDTYDNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-羟基吡啶 、 3-(2-chloroacetamino)-7,8-dehydrorutaecarpine 反应 8.0h， 以98%的产率得到3-(2-(pyridin-3-yloxy)-acetamino)-7,8-dehydrorutaecarpine
  参考文献：
  名称：

  Synthesis and evaluation of 7,8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease

  摘要：

  A series of 7,8-dehydrorutaecarpine derivatives were synthesized and characterized as potential multifunctional agents for treatment of Alzheimer's disease (AD). All of these synthetic compounds showed high acetylcholinesterase (AChE) inhibitory activity with IC50 values ranged from 0.60 to 196.7 nM, and good selectivity for AChE over butyrylcholinesterase (BuChE) (125- to 3225-fold). A Lineweaver-Burk plot and molecular modeling study indicated these compounds could bind to both catalytic active site and the peripheral anionic site of AChE. Besides, compounds showed higher activity of inhibiting AChE-induced amyloid-beta (A beta) aggregation than curcumin, higher anti-oxidative activity than Trolox, and could also be good metal chelators. Considering their low cytotoxicity, our results indicated that these derivatives provide good templates for developing new multifunctional agents for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.014
• 作为产物：
  描述：

  3-amino-rutaecarpine 在 potassium carbonate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 12.5h， 生成 3-(2-chloroacetamino)-7,8-dehydrorutaecarpine
  参考文献：
  名称：

  Synthesis and evaluation of 7,8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease

  摘要：

  A series of 7,8-dehydrorutaecarpine derivatives were synthesized and characterized as potential multifunctional agents for treatment of Alzheimer's disease (AD). All of these synthetic compounds showed high acetylcholinesterase (AChE) inhibitory activity with IC50 values ranged from 0.60 to 196.7 nM, and good selectivity for AChE over butyrylcholinesterase (BuChE) (125- to 3225-fold). A Lineweaver-Burk plot and molecular modeling study indicated these compounds could bind to both catalytic active site and the peripheral anionic site of AChE. Besides, compounds showed higher activity of inhibiting AChE-induced amyloid-beta (A beta) aggregation than curcumin, higher anti-oxidative activity than Trolox, and could also be good metal chelators. Considering their low cytotoxicity, our results indicated that these derivatives provide good templates for developing new multifunctional agents for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.014

文献信息

• Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors
  作者：Bin Wang、Yi-Chi Mai、Yue Li、Jin-Qiang Hou、Shi-Liang Huang、Tian-Miao Ou、Jia-Heng Tan、Lin-Kun An、Ding Li、Lian-Quan Gu

  DOI：10.1016/j.ejmech.2009.12.044

  日期：2010.4

  A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a–f and 7,8-dehydrorutaecarpine 5a–c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a–c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds exhibited strong inhibitory activity

  一系列新的芸香芸香碱衍生物和相关生物碱衍生物3-氨基烷酰胺基取代的芸香芸香碱4a - f和7,8-脱氢芸苔芸香碱5a - c，以及6-氨基烷酰胺基取代的3- [2-（3-吲哚基）乙基] -4（合成了3a）-喹唑啉酮8a – c，并作为乙酰胆碱酯酶（AChE）抑制剂进行了药理学评估。与BuChE相比，合成化合物对AChE表现出强大的抑制活性，对AChE具有高选择性。讨论了结构-活性关系，并通过动力学表征和分子对接研究进一步阐明了它们的结合构象和同时相互作用模式。