2-allylsulfanyl-3-methoxybenzaldehyde | 805246-33-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-allylsulfanyl-3-methoxybenzaldehyde
• 英文别名: 3-methoxy-2-prop-2-enylsulfanylbenzaldehyde
• CAS: 805246-33-7
• 化学式: C₁₁H₁₂O₂S
• 分子量: 208.281
• InChiKey: KAYQWYOMCJNVRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-allylsulfanyl-3-methoxybenzaldehyde 在 三甲基氯硅烷 、 三溴化硼 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 45.0h， 生成 cis-methylcarbamic acid 1-methyl-2,3,3a,4,5,9b-hexahydro-5-thia-1-azacyclopenta[a]naphthalen-6-yl ester
  参考文献：
  名称：

  设计，合成和生物评价构象受限的rivastigmine类似物。

  摘要：

  Rivastigmine（1）是一种2000年批准用于治疗阿尔茨海默氏病的乙酰胆碱酯酶（AChE）抑制剂，其结构中具有氨基甲酸酯部分，能够与该酶的活性位点共价反应。关于1与不同的胆碱酯酶相互作用的动力学和结构研究已经发表，对催化机理提供了更深入但不确定的见解。基于这些发现，并结合我们先前对一系列苯并吡喃并[4,3-b]吡咯氨基甲酸酯作为AChE抑制剂的研究，我们通过包括二甲基氨基-α-甲基苄基部分设计了一系列构象受限的1类似物在不同的三环系统中 从蒙特卡洛模拟中获得的1与碳衍生物4的构型之间的叠加，支持三环衍生物可能充当1的刚性类似物的想法。体外抗人AChE和BChE评估的4-9生物学特性验证了我们的合理设计。具有含硫系统的化合物5表现出最高的抑制活性，比1的效力高192倍。在本研究中，最有效的抑制剂始终是甲基衍生物3-5，具有纳摩尔范围的效力，而乙基的效价低40倍。对于这一发现的合理解释

  DOI：

  10.1021/jm049782n
• 作为产物：
  描述：

  O-(2-formyl-6-methoxyphenyl) dimethylcarbamothioate 在 sodium hydroxide 、 二苯醚 作用下， 生成 2-allylsulfanyl-3-methoxybenzaldehyde
  参考文献：
  名称：

  Heterocyclic inhibitors of AChE acylation and peripheral sites

  摘要：

  Notwithstanding the criticism to the so called " cholinergic hypothesis", the therapeutic strategies for the treatment of Alzheimer's disease (AD) have been mainly centered on the restoration of cholinergic functionality and, until the last year, the only drugs licensed for the management of AD were the acetycholinesterase (AChE) inhibitors. Target enzyme AChE consists of a narrow gorge with two separate ligand binding sites: an acylation site at the bottom of the gorge containing the catalytic triad and a peripheral site located at the gorge rim, which encompasses binding sites for allosteric ligands. The aim of this short review is to update the knowledge on heterocyclic AChE inhibitors able to interact with the two sites of enzymes, structurally related to the well known inhibitors physostigmine, rivastigmine and propidium. The therapeutic potential of the dual site inhibithors in inhibiting amyloid-beta aggregatrion and deposition is also briefly summarised.

  DOI：

  10.1016/j.farmac.2005.03.010

文献信息

• Design, Synthesis, and Biological Evaluation of Conformationally Restricted Rivastigmine Analogues
  作者：Maria Laura Bolognesi、Manuela Bartolini、Andrea Cavalli、Vincenza Andrisano、Michela Rosini、Anna Minarini、Carlo Melchiorre

  DOI：10.1021/jm049782n

  日期：2004.11.1

  carbamates as AChE inhibitors, we designed a series of conformationally restricted analogues of 1 by including the dimethylamino-alpha-methylbenzyl moiety in different tricyclic systems. A superimposition between the conformation of 1 and the carbon derivative 4, as obtained from Monte Carlo simulations, supported the idea that the tricyclic derivatives might act as rigid analogues of 1. The biological profile

  Rivastigmine（1）是一种2000年批准用于治疗阿尔茨海默氏病的乙酰胆碱酯酶（AChE）抑制剂，其结构中具有氨基甲酸酯部分，能够与该酶的活性位点共价反应。关于1与不同的胆碱酯酶相互作用的动力学和结构研究已经发表，对催化机理提供了更深入但不确定的见解。基于这些发现，并结合我们先前对一系列苯并吡喃并[4,3-b]吡咯氨基甲酸酯作为AChE抑制剂的研究，我们通过包括二甲基氨基-α-甲基苄基部分设计了一系列构象受限的1类似物在不同的三环系统中 从蒙特卡洛模拟中获得的1与碳衍生物4的构型之间的叠加，支持三环衍生物可能充当1的刚性类似物的想法。体外抗人AChE和BChE评估的4-9生物学特性验证了我们的合理设计。具有含硫系统的化合物5表现出最高的抑制活性，比1的效力高192倍。在本研究中，最有效的抑制剂始终是甲基衍生物3-5，具有纳摩尔范围的效力，而乙基的效价低40倍。对于这一发现的合理解释
• Heterocyclic inhibitors of AChE acylation and peripheral sites
  作者：Maria Laura Bolognesi、Vincenza Andrisano、Manuela Bartolini、Andrea Cavalli、Anna Minarini、Maurizio Recanatini、Michela Rosini、Vincenzo Tumiatti、Carlo Melchiorre

  DOI：10.1016/j.farmac.2005.03.010

  日期：2005.6

  Notwithstanding the criticism to the so called " cholinergic hypothesis", the therapeutic strategies for the treatment of Alzheimer's disease (AD) have been mainly centered on the restoration of cholinergic functionality and, until the last year, the only drugs licensed for the management of AD were the acetycholinesterase (AChE) inhibitors. Target enzyme AChE consists of a narrow gorge with two separate ligand binding sites: an acylation site at the bottom of the gorge containing the catalytic triad and a peripheral site located at the gorge rim, which encompasses binding sites for allosteric ligands. The aim of this short review is to update the knowledge on heterocyclic AChE inhibitors able to interact with the two sites of enzymes, structurally related to the well known inhibitors physostigmine, rivastigmine and propidium. The therapeutic potential of the dual site inhibithors in inhibiting amyloid-beta aggregatrion and deposition is also briefly summarised.