3-amino-13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine | 1224467-41-7

• 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-amino-13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine
• 英文别名: 17-Amino-1-(trifluoromethyl)-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-14-one
• CAS: 1224467-41-7
• 化学式: C₁₉H₁₅F₃N₄O
• 分子量: 372.35
• InChiKey: RHJNTTYTKYUCPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-amino-13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 61.0h， 生成 3-(2-phenyl-butyramino)-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-nitro-13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以80%的产率得到3-amino-13b-(trifluoromethyl)-13b,14-dihydrorutaecarpine
  参考文献：
  名称：

  新型芸苔芸香碱衍生物和相关生物碱衍生物作为选择性乙酰胆碱酯酶抑制剂的合成与评价

  摘要：

  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。

  DOI：

  10.1016/j.ejmech.2009.12.044

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。
• 一种3-胺基磺酰胺基取代的吴茱萸次碱类衍 生物及其制备方法和应用
  申请人：安徽医科大学

  公开号：CN109761980B

  公开（公告）日：2020-11-24

  本发明公开了一种3‑胺基磺酰胺基取代的吴茱萸次碱类衍生物及其制备方法和应用，属于药物化学技术领域，其中所涉及的3‑胺基磺酰胺基取代的吴茱萸次碱类衍生物对丁酰胆碱酯酶具有很强的抑制性能及很好的抑制选择性，其对丁酰胆碱酯酶的抑制能力比对乙酰胆碱酯酶的抑制活性高出20多倍，表明该类化合物能够发展成为治疗阿尔茨海默症的药物。
• Design, synthesis, and biological evaluation of rutacecarpine derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease
  作者：Mingfei Wu、Jie Ma、Lijun Ji、Min Wang、Jianfei Han、Zeng Li

  DOI：10.1016/j.ejmech.2019.05.055

  日期：2019.9

  synthesized to identify novel multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). Biological evaluation showed that most of the synthesized compounds inhibited butyrylcholinesterase (BuChE) and exerted antioxidant effects. Among the synthesized compounds, 6n was subjected to further biological evaluation. Lineweaver–Burk plotting and molecular modeling illustrated that 6n

  合成了一系列3-氨基取代的芸香芸香碱衍生物，以鉴定用于治疗阿尔茨海默氏病（AD）的新型多靶标配体（MTDL）。生物学评估表明，大多数合成的化合物均抑制丁酰胆碱酯酶（BuChE）并发挥抗氧化作用。在合成的化合物中，对6n进行了进一步的生物学评估。Lineweaver-Burk绘图和分子建模表明6n同时与BuChE的外围阴离子位点（PAS）和催化位点（CAS）结合。此外，6n调节的Aβ聚集；螯合生物金属 表现出良好的吸收，分布，代谢，排泄和毒性。并显示出显着的神经保护活性。先前的研究表明，优化的化合物6n作为用于治疗AD的MTDL具有很大的开发潜力。
• Synthesis and evaluation of 7,8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease
  作者：Yan He、Pei-Fen Yao、Shuo-bin Chen、Zhi-hong Huang、Shi-Liang Huang、Jia-Heng Tan、Ding Li、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.1016/j.ejmech.2013.02.014

  日期：2013.5

  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.