2-{4-[(benzylmethylamino)methyl]benzylidene}-6-(5-diethylaminopentyloxy)indan-1-one | 1224099-31-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-{4-[(benzylmethylamino)methyl]benzylidene}-6-(5-diethylaminopentyloxy)indan-1-one
• 英文别名: 2-[[4-[[benzyl(methyl)amino]methyl]phenyl]methylidene]-6-[5-(diethylamino)pentoxy]-3H-inden-1-one
• CAS: 1224099-31-3
• 化学式: C₃₄H₄₂N₂O₂
• 分子量: 510.72
• InChiKey: BHEFQVICVNMJDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.03
• 重原子数：
  38.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.78
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  2-{4-[(benzylmethylamino)methyl]benzylidene}-6-(5-iodopentyloxy)indan-1-one 、 二乙胺 以 甲苯 为溶剂， 反应 20.0h， 以11%的产率得到2-{4-[(benzylmethylamino)methyl]benzylidene}-6-(5-diethylaminopentyloxy)indan-1-one
  参考文献：
  名称：

  Targeting Alzheimer’s disease: Novel indanone hybrids bearing a pharmacophoric fragment of AP2238

  摘要：

  We report on a series of hybrid compounds structurally derived from donepezil and AP2238. This study was aimed at improving the activities of the reference compounds, donepezil and AP2238, and at broadening the range of activities of new derivatives as, due to the multifactorial nature of AD, molecules that modulate the activity of a single protein target are unable to significantly modify the progression of the disease. In particular, the indanone core from donepezil was linked to the phenyl-N-methylbenzylamino moiety from AP2238, through a double bond that was kept to evaluate the role of a lower flexibility in the biological activities. Moreover, SAR studies were performed to evaluate the role of different substituents in position 5 or 6 of the indanone ring in the interaction with the PAS, introducing also alkyl chains of different lengths carrying different amines at one end. Derivatives 21 and 22 proved to be the most active within the series and their potencies against AChE were in the same order of magnitude of the reference compounds. Compounds 15, 21-22, with a 5-carbon alkyl chain bearing an amino moiety at one end, better contacting the PAS, remarkably improved the inhibition of AChE-induced A beta aggregation with respect to the reference compounds. They also showed activity against self-aggregation of A beta(42) peptide, the most amyloidogenic form of amyloid produced in AD brains, while the reference compounds resulted completely ineffective. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.071

文献信息

• Targeting Alzheimer’s disease: Novel indanone hybrids bearing a pharmacophoric fragment of AP2238
  作者：Stefano Rizzo、Manuela Bartolini、Luisa Ceccarini、Lorna Piazzi、Silvia Gobbi、Andrea Cavalli、Maurizio Recanatini、Vincenza Andrisano、Angela Rampa

  DOI：10.1016/j.bmc.2010.01.071

  日期：2010.3

  We report on a series of hybrid compounds structurally derived from donepezil and AP2238. This study was aimed at improving the activities of the reference compounds, donepezil and AP2238, and at broadening the range of activities of new derivatives as, due to the multifactorial nature of AD, molecules that modulate the activity of a single protein target are unable to significantly modify the progression of the disease. In particular, the indanone core from donepezil was linked to the phenyl-N-methylbenzylamino moiety from AP2238, through a double bond that was kept to evaluate the role of a lower flexibility in the biological activities. Moreover, SAR studies were performed to evaluate the role of different substituents in position 5 or 6 of the indanone ring in the interaction with the PAS, introducing also alkyl chains of different lengths carrying different amines at one end. Derivatives 21 and 22 proved to be the most active within the series and their potencies against AChE were in the same order of magnitude of the reference compounds. Compounds 15, 21-22, with a 5-carbon alkyl chain bearing an amino moiety at one end, better contacting the PAS, remarkably improved the inhibition of AChE-induced A beta aggregation with respect to the reference compounds. They also showed activity against self-aggregation of A beta(42) peptide, the most amyloidogenic form of amyloid produced in AD brains, while the reference compounds resulted completely ineffective. (C) 2010 Elsevier Ltd. All rights reserved.