ethyl 5-(4-chlorophenyl)-3,4-dihydro-2H-pyrano[3,2-c]quinoline-9-carboxylate | 1185886-12-7

• 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: ethyl 5-(4-chlorophenyl)-3,4-dihydro-2H-pyrano[3,2-c]quinoline-9-carboxylate
• 英文别名: tricyclic ester, 11.HCl
• CAS: 1185886-12-7
• 化学式: C₂₁H₁₈ClNO₃
• 分子量: 367.832
• InChiKey: ARWPWQWERJBZLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 5-(4-chlorophenyl)-3,4-dihydro-2H-pyrano[3,2-c]quinoline-9-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 生成 5-(4-chlorophenyl)-3,4-dihydro-2H-pyrano[3,2-c]quinoline-9-carboxylic acid;hydrochloride
  参考文献：
  名称：

  Pyrano[3,2-c]quinoline−6-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and β-Amyloid-Directed Anti-Alzheimer Compounds

  摘要：

  Two isomeric series of dual binding site acetyleholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced and self-induced beta-amyloid (A beta) aggregation, and beta-secretase (BACE-1) and to cross blood-brain barrier. The new hybrids consist of a unit of 6-chlorotacrine and a multicomponent reaction-derived pyrano[3,2-c]-quinoline scaffold as the active-site and peripheral-site interacting moieties, respectively, connected through an oligomethylene linker containing an amido group at variable position. Indeed, molecular modeling and kinetic studies have confirmed the dual site binding of these compounds. The new hybrids, and particularly 27, retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitory activity toward the AChE-induced and self-induced A beta aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.

  DOI：

  10.1021/jm900859q
• 作为产物：
  描述：

  (4aRS,5RS,10bRS)- and (4aRS,5SR,10bRS)-ethyl 5-(4-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline-9-carboxylate 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以75%的产率得到ethyl 5-(4-chlorophenyl)-3,4-dihydro-2H-pyrano[3,2-c]quinoline-9-carboxylate
  参考文献：
  名称：

  Pyrano[3,2-c]quinoline−6-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and β-Amyloid-Directed Anti-Alzheimer Compounds

  摘要：

  Two isomeric series of dual binding site acetyleholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced and self-induced beta-amyloid (A beta) aggregation, and beta-secretase (BACE-1) and to cross blood-brain barrier. The new hybrids consist of a unit of 6-chlorotacrine and a multicomponent reaction-derived pyrano[3,2-c]-quinoline scaffold as the active-site and peripheral-site interacting moieties, respectively, connected through an oligomethylene linker containing an amido group at variable position. Indeed, molecular modeling and kinetic studies have confirmed the dual site binding of these compounds. The new hybrids, and particularly 27, retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitory activity toward the AChE-induced and self-induced A beta aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.

  DOI：

  10.1021/jm900859q

文献信息

• Pyrano[3,2-<i>c</i>]quinoline−6-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and β-Amyloid-Directed Anti-Alzheimer Compounds
  作者：Pelayo Camps、Xavier Formosa、Carles Galdeano、Diego Muñoz-Torrero、Lorena Ramírez、Elena Gómez、Nicolás Isambert、Rodolfo Lavilla、Albert Badia、M. Victòria Clos、Manuela Bartolini、Francesca Mancini、Vincenza Andrisano、Mariana P. Arce、M. Isabel Rodríguez-Franco、Óscar Huertas、Thomai Dafni、F. Javier Luque

  DOI：10.1021/jm900859q

  日期：2009.9.10

  Two isomeric series of dual binding site acetyleholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced and self-induced beta-amyloid (A beta) aggregation, and beta-secretase (BACE-1) and to cross blood-brain barrier. The new hybrids consist of a unit of 6-chlorotacrine and a multicomponent reaction-derived pyrano[3,2-c]-quinoline scaffold as the active-site and peripheral-site interacting moieties, respectively, connected through an oligomethylene linker containing an amido group at variable position. Indeed, molecular modeling and kinetic studies have confirmed the dual site binding of these compounds. The new hybrids, and particularly 27, retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitory activity toward the AChE-induced and self-induced A beta aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.