3-(((N-(3-(2H-2-oxochromen-7-yl)oxymethyl)benzyl)-N-methylamino)methyl)benzonitrile hydrochloride

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-(((N-(3-(2H-2-oxochromen-7-yl)oxymethyl)benzyl)-N-methylamino)methyl)benzonitrile hydrochloride
• 英文别名: 3-[[Methyl-[[3-[(2-oxochromen-7-yl)oxymethyl]phenyl]methyl]amino]methyl]benzonitrile;hydrochloride；3-[[methyl-[[3-[(2-oxochromen-7-yl)oxymethyl]phenyl]methyl]amino]methyl]benzonitrile;hydrochloride
• 化学式: C₂₆H₂₂N₂O₃*ClH
• 分子量: 446.933
• InChiKey: OMTVFRBSDXUJDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  间二溴苄 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 3-(((N-(3-(2H-2-oxochromen-7-yl)oxymethyl)benzyl)-N-methylamino)methyl)benzonitrile hydrochloride
  参考文献：
  名称：

  Structure-Based Design and Optimization of Multitarget-Directed 2H-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases

  摘要：

  The multifactorial nature of Alzheimer's disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta-and para-xylyl linkers, displayed: good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring art improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.

  DOI：

  10.1021/acs.jmedchem.5b00599

文献信息

• Structure-Based Design and Optimization of Multitarget-Directed 2<i>H</i>-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases
  作者：Roberta Farina、Leonardo Pisani、Marco Catto、Orazio Nicolotti、Domenico Gadaleta、Nunzio Denora、Ramon Soto-Otero、Estefania Mendez-Alvarez、Carolina S. Passos、Giovanni Muncipinto、Cosimo D. Altomare、Alessandra Nurisso、Pierre-Alain Carrupt、Angelo Carotti

  DOI：10.1021/acs.jmedchem.5b00599

  日期：2015.7.23

  The multifactorial nature of Alzheimer's disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta-and para-xylyl linkers, displayed: good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring art improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.