6-(2-aminoethoxy)-3-{4-[(benzylethylamino)methyl]phenyl}-chromen-2-one | 1008798-53-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 6-(2-aminoethoxy)-3-{4-[(benzylethylamino)methyl]phenyl}-chromen-2-one
• CAS: 1008798-53-5
• 化学式: C₂₇H₂₈N₂O₃
• 分子量: 428.531
• InChiKey: WPSFGLNGMXSHOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.82
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  68.7
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6-(2-aminoethoxy)-3-{4-[(benzylethylamino)methyl]phenyl}-chromen-2-one 、 3,5-difluorocinnamic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-[2-(3-{4-[(benzylethylamino)methyl]phenyl}-2-oxo-2H-chromen-6-yloxy)ethyl]3-(3,5-difluorophenyl)acrylamide
  参考文献：
  名称：

  Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds

  摘要：

  The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.09.100
• 作为产物：
  描述：

  [2-(3-{4-[(benzylethylamino)methyl]phenyl}-2-oxo-2H-chromen-6-yloxy)ethyl]carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以86%的产率得到6-(2-aminoethoxy)-3-{4-[(benzylethylamino)methyl]phenyl}-chromen-2-one
  参考文献：
  名称：

  Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds

  摘要：

  The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.09.100

文献信息

• Multitarget Strategy to Address Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and Computational Studies of Coumarin-Based Derivatives
  作者：Serena Montanari、Manuela Bartolini、Paolo Neviani、Federica Belluti、Silvia Gobbi、Letizia Pruccoli、Andrea Tarozzi、Federico Falchi、Vincenza Andrisano、Przemysław Miszta、Andrea Cavalli、Sławomir Filipek、Alessandra Bisi、Angela Rampa

  DOI：10.1002/cmdc.201500392

  日期：2016.6.20

  substitution pattern at the 6‐ or 7‐position was modified by introducing alkyl chains of variable lengths and with different terminal amino functional groups. 3‐(4‐[Benzyl(ethyl)amino]methyl}phenyl)‐6‐(5‐[(7‐methoxy‐6H‐indeno[2,1‐b]quinolin‐11‐yl)amino]pentyl}oxy)‐2H‐chromen‐2‐one, bearing the bulkiest amine, emerged as a non‐neurotoxic dual acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) inhibitor

  阿尔茨海默氏病（AD）是面临着全球人口老龄化的主要公共卫生挑战。当前的药物治疗仅表现出对症治疗功效，对新一代疾病缓解疗法的医疗需求仍未得到满足。遵循多目标导向的配体方法，设计并合成了一个小小的基于香豆素的衍生物库，作为我们对AP2238的研究的后续研究，旨在扩大其生物学特性。通过引入长度可变且具有不同末端氨基官能团的烷基链，可以修饰6或7位的香豆素取代方式。3-（4-（[[苄基（乙基）氨基]甲基}苯基）苯基-6-（5-[（7-甲氧基-6 H-茚并[2,1 - b ]喹啉-11-基）氨基]戊基} oxy）-2 H带有最多胺的-2-铬-2-酮以非神经毒性双重乙酰胆碱酯酶（AChE）/丁酰胆碱酯酶（BuChE）抑制剂的形式出现，可能适合治疗AD的中期。此外，引入了二乙基氨基的间隔物，如3-（4 - [苄基（乙基）氨基]甲基}苯基）-6 - [5-（二乙基氨基）戊基]氧基} -2- ħ -苯并吡喃-2-