N-{10-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-6,7-dihydroxy-4-oxo-4H-chromene-2-carboxamide hydrochloride | 1356925-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-{10-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-6,7-dihydroxy-4-oxo-4H-chromene-2-carboxamide hydrochloride
• 英文别名: N-[10-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl]-6,7-dihydroxy-4-oxochromene-2-carboxamide;hydrochloride
• CAS: 1356925-86-4
• 化学式: C₃₃H₃₇Cl₂N₃O₅*ClH
• 分子量: 663.041
• InChiKey: GLTZVNFMJVLGST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.32
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  121
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid 在 盐酸 、 三溴化硼 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 N-{10-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-6,7-dihydroxy-4-oxo-4H-chromene-2-carboxamide hydrochloride
  参考文献：
  名称：

  New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

  摘要：

  By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a new family of tacrine-4-oxo-4H-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H-chromene was chosen for its radical capture and beta-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine-4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-{10-[(1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-4 H-chromene-2-carboxamide (19) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties.

  DOI：

  10.1021/jm201460y

文献信息

• New Tacrine–4-Oxo-4<i>H</i>-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties
  作者：María Isabel Fernández-Bachiller、Concepción Pérez、Leticia Monjas、Jörg Rademann、María Isabel Rodríguez-Franco

  DOI：10.1021/jm201460y

  日期：2012.2.9

  By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a new family of tacrine-4-oxo-4H-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H-chromene was chosen for its radical capture and beta-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine-4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-10-[(1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-4 H-chromene-2-carboxamide (19) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties.