2-benzyl-2-[2-(dimethylamino)ethyl]malonic acid diethyl ester | 1805-03-4

• 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-benzyl-2-[2-(dimethylamino)ethyl]malonic acid diethyl ester
• 英文别名: benzyl-(2-dimethylamino-ethyl)-malonic acid diethyl ester；Benzyl-(2-dimethylamino-aethyl)-malonsaeure-diaethylester；Benzyl-<2-dimethylamino-aethyl>-malonsaeure-diaethylester；Diethyl 2-benzyl-2-(2-(dimethylamino)ethyl)malonate；diethyl 2-benzyl-2-[2-(dimethylamino)ethyl]propanedioate
• CAS: 1805-03-4
• 化学式: C₁₈H₂₇NO₄
• 分子量: 321.417
• InChiKey: ACKPFPBDEOFVIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyl-2-[2-(dimethylamino)ethyl]malonic acid diethyl ester 在 硝基甲烷 、 水 、 silver(l) oxide 作用下， 生成 3-benzyl-2-oxo-tetrahydro-furan-3-carboxylic acid
  参考文献：
  名称：

  160.极和极连接对消除反应所遵循的过程的影响。第二十二部分。霍夫曼退化中的瓦格纳重排

  摘要：

  DOI：

  10.1039/jr9350000722
• 作为产物：
  描述：

  苄基丙二酸二乙酯 在 sodium 、 xylene 作用下， 生成 2-benzyl-2-[2-(dimethylamino)ethyl]malonic acid diethyl ester
  参考文献：
  名称：

  160.极和极连接对消除反应所遵循的过程的影响。第二十二部分。霍夫曼退化中的瓦格纳重排

  摘要：

  DOI：

  10.1039/jr9350000722

文献信息

• Structure−Activity Relationships of Dimethindene Derivatives as New M₂-Selective Muscarinic Receptor Antagonists
  作者：Thomas M. Böhme、Christine Keim、Kai Kreutzmann、Matthias Linder、Theo Dingermann、Gerd Dannhardt、Ernst Mutschler、Günter Lambrecht

  DOI：10.1021/jm020895l

  日期：2003.2.1

  A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H, receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M-1-M-5) and for human histamine H, receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [H-3]N-methylscopolamine ([H-3]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M-2 receptors ((S)-dimethindene: pK(i) = 7.52; (-)-19: pK(i) = 7.37) with an improved selectivity pattern ((S)-dimethindene: M-2/M-1 = 6-fold, M-2/M-3 = 5-fold, M-2/M-4 = 10-fold, M-2/M-5 = 25-fold; (-)-19: M-2/M-1 = 36-fold, M-2/M-3 = 96-fold, M-2/M-4 = 42-fold, M-2/M-5 = 275-fold). In addition, compound (-)-19 showed 35-fold lower affinity at histamine H-1 receptors (pK(i) = 5.61) than (S)-dimethindene (pK(i) = 7.16). Another interesting compound is the fluoroethyl derivative 20 (pK(i)/M-2 = 7.49), which also exhibits a higher M-2 selectivity (M-2/M-1 = 19-fold; M-2/M-3 = 22-fold; M-2/M-4 = 13-fold; M-2/ M-5 = 62-fold) than (S)-dimethindene. Unfortunately, compound 20 also shows a high affinity for histamine H-1 receptors (pK(i) = 8.14). The compound with the highest affinity for M-2 receptors (pK(i) = 7.91), the dimethylaminomethylene analogue 31, displayed only a small preference for M-2 receptors. In conclusion, compound (-)-19 might be useful to test the hypothesis that blockade of muscarinic M-2 receptors in the brain is a viable mechanism by which to produce improved cognition. This second-generation dimethindene analogue might also be the starting point for the development Of M-2-selective muscarinic antagonists useful for quantifying M-2 receptors in the central nervous system with positron emission tomography imaging.
• Notes - Anomalous Hofmann Elimination Reactions
  作者：M. A. Rogers

  DOI：10.1021/jo01354a623

  日期：1957.3
• 160. Influence of poles and polar linkings on the course pursued by elimination reactions. Part XXII. Wagner rearrangement in the Hofmann degradation
  作者：Christopher K. Ingold、Maurice A. T. Rogers

  DOI：10.1039/jr9350000722

  日期：——