3-(6-chlorohexyloxy)xanthen-9-one | 380363-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-(6-chlorohexyloxy)xanthen-9-one
• 英文别名: 3-(6-Chlorohexoxy)xanthen-9-one
• CAS: 380363-89-3
• 化学式: C₁₉H₁₉ClO₃
• 分子量: 330.811
• InChiKey: MVCSOCNCQBFFMV-UHFFFAOYSA-N

物化性质

• 熔点：
  96-97 °C
• 沸点：
  486.6±45.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(6-chlorohexyloxy)xanthen-9-one 在 sodium iodide 作用下， 以 甲苯 、 丁酮 为溶剂， 反应 19.0h， 生成 3-[[[N-methyl-N-(3-hydroxybenzyl)amino]hexyl]oxy]xanthen-9-one
  参考文献：
  名称：

  Acetylcholinesterase Inhibitors:  SAR and Kinetic Studies on ω-[N-Methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl Derivatives

  摘要：

  In this work, we further investigated a class of carbamic cholinesterase inhibitors introduced in a previous paper (Rampa et al. J. Med. Chem. 1998, 41, 3976). Some new omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl analogues were designed, synthesized, and evaluated for their inhibitory activity against both acetyleholinesterase (AChE) and butyrylcholinesterase (BuChE). The structure of the lead compound (xanthostigmine) was systematically varied with the aim to optimize the different parts of the molecule. Moreover, such a structure-activity relationships (SAR) study was integrated with a kinetic analysis of the mechanism of AChE inhibition for two representative compounds. The structural modifications lead to a compound (12b) showing an IC50 value for the AChE inhibition of 0.32 +/- 0.09 nM and to a group of BuChE inhibitors also active at the nanomolar level, the most potent of which (15d) was characterized by an IC50 value of 3.3 +/- 0.4 nM. The kinetic analysis allowed for clarification of the role played by different molecular moieties with regard to the rate of AChE carbamoylation and the duration of inhibition. On the basis of the results presented here, it was concluded that the cholinesterase inhibitors of this class possess promising characteristics in view of a potential development as drugs for the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm010914b
• 作为产物：
  描述：

  1-溴-6-氯己烷 、 西伯尔链接剂 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以80%的产率得到3-(6-chlorohexyloxy)xanthen-9-one
  参考文献：
  名称：

  Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-ones

  摘要：

  In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbarnic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000-fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.026

文献信息

• Acetylcholinesterase Inhibitors:  SAR and Kinetic Studies on ω-[<i>N</i>-Methyl-<i>N</i>-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl Derivatives
  作者：Angela Rampa、Lorna Piazzi、Federica Belluti、Silvia Gobbi、Alessandra Bisi、Manuela Bartolini、Vincenza Andrisano、Vanni Cavrini、Andrea Cavalli、Maurizio Recanatini、Piero Valenti

  DOI：10.1021/jm010914b

  日期：2001.11.1

  In this work, we further investigated a class of carbamic cholinesterase inhibitors introduced in a previous paper (Rampa et al. J. Med. Chem. 1998, 41, 3976). Some new omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl analogues were designed, synthesized, and evaluated for their inhibitory activity against both acetyleholinesterase (AChE) and butyrylcholinesterase (BuChE). The structure of the lead compound (xanthostigmine) was systematically varied with the aim to optimize the different parts of the molecule. Moreover, such a structure-activity relationships (SAR) study was integrated with a kinetic analysis of the mechanism of AChE inhibition for two representative compounds. The structural modifications lead to a compound (12b) showing an IC50 value for the AChE inhibition of 0.32 +/- 0.09 nM and to a group of BuChE inhibitors also active at the nanomolar level, the most potent of which (15d) was characterized by an IC50 value of 3.3 +/- 0.4 nM. The kinetic analysis allowed for clarification of the role played by different molecular moieties with regard to the rate of AChE carbamoylation and the duration of inhibition. On the basis of the results presented here, it was concluded that the cholinesterase inhibitors of this class possess promising characteristics in view of a potential development as drugs for the treatment of Alzheimer's disease.
• Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-ones
  作者：Lorna Piazzi、Federica Belluti、Alessandra Bisi、Silvia Gobbi、Stefano Rizzo、Manuela Bartolini、Vincenza Andrisano、Maurizio Recanatini、Angela Rampa

  DOI：10.1016/j.bmc.2006.09.026

  日期：2007.1.1

  In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbarnic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000-fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases. (c) 2006 Elsevier Ltd. All rights reserved.