N-{10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-5,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide | 1356992-65-8

• 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-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-5,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide
• 英文别名: N-[10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl]-5,7-dimethoxy-4-oxochromene-2-carboxamide
• CAS: 1356992-65-8
• 化学式: C₃₅H₄₂ClN₃O₅
• 分子量: 620.189
• InChiKey: DWXXMYCVGFGBCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-{10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-5,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide 在 盐酸 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 N-{10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-5-hydroxy-7-methoxy-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
• 作为产物：
  描述：

  6-chloro-9-(10-aminodecylamino)-1,2,3,4-tetrahydroacridine 、 5,7-dimethoxy-4-oxo-4H-chromene-2-carboxylic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以118 mg的产率得到N-{10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-5,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide
  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