2-<2-(dimethylamino)-ethyl>-5-methoxy-indane-1-one | 173070-28-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-<2-(dimethylamino)-ethyl>-5-methoxy-indane-1-one
• 英文别名: 2-[2-(dimethylamino)ethyl]-5-methoxyindan-1-one；2-(2-dimethylamino-ethyl)-5-methoxy-indan-l-one；2-[2-(Dimethylamino)ethyl]-2,3-dihydro-5-methoxy-1H-inden-1-one；2-[2-(dimethylamino)ethyl]-5-methoxy-2,3-dihydroinden-1-one
• CAS: 173070-28-5
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: KNYFXBDLDVROFU-UHFFFAOYSA-N

物化性质

• 沸点：
  359.5±35.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-<2-(dimethylamino)-ethyl>-5-methoxy-indane-1-one 在 盐酸 、 氢溴酸 、 1,8-双二甲氨基萘 、 苯基锂 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 11.0h， 生成 6-羟基-N-去甲基二甲叉
  参考文献：
  名称：

  Radler; Wermeille; Blaschke, Arzneimittel-Forschung/Drug Research, 1995, vol. 45, # 10, p. 1086 - 1092

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(2-(dimethylamino)ethyl)-5-methoxy-2,3-dihydro-1H-inden-1-ol 在 二苯甲酮 、 potassium tert-butylate 作用下， 以 苯 为溶剂， 生成 2-<2-(dimethylamino)-ethyl>-5-methoxy-indane-1-one
  参考文献：
  名称：

  新型茚H 1-抗组胺药治疗失眠症的选择性分析

  摘要：

  在寻找潜在改善的镇静催眠药的过程中，评估了H 1-抗组胺（-）- R-二甲基茚的一系列茚类似物的选择性。茚核心中6位取代基与丰富的电子侧链结合的变化导致鉴定出几种有效的H 1-抗组胺药，它们对CYP酶，M 1毒蕈碱受体和hERG通道具有理想的选择性。这些化合物是进一步ADME分析和体内评估的候选药物。

  DOI：

  10.1016/j.bmcl.2010.02.055

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.
• Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia
  作者：Wilna J. Moree、Bin-Feng Li、Said Zamani-Kord、Jinghua Yu、Timothy Coon、Charles Huang、Dragan Marinkovic、Fabio C. Tucci、Siobhan Malany、Margaret J. Bradbury、Lisa M. Hernandez、Jianyun Wen、Hua Wang、Samuel R.J. Hoare、Robert E. Petroski、Kayvon Jalali、Chun Yang、Aida Sacaan、Ajay Madan、Paul D. Crowe、Graham Beaton

  DOI：10.1016/j.bmcl.2010.07.117

  日期：2010.10

  Analogs of the known H-1-antihistamine R-dimethindene with suitable selectivity for key GPCRs, P450 enzymes and hERG channel were assessed for metabolism profile and in vivo properties. Several analogs were determined to exhibit diverse metabolism. One of these compounds, 10a, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate and a potentially superior pharmacokinetic profile as determined from a human microdose study. (C) 2010 Elsevier Ltd. All rights reserved.
• Selectivity profiling of novel indene H1-antihistamines for the treatment of insomnia
  作者：Bin-Feng Li、Wilna J. Moree、Jinghua Yu、Timothy Coon、Said Zamani-Kord、Siobhan Malany、Kayvon Jalali、Jianyun Wen、Hua Wang、Chun Yang、Samuel R.J. Hoare、Robert E. Petroski、Ajay Madan、Paul D. Crowe、Graham Beaton

  DOI：10.1016/j.bmcl.2010.02.055

  日期：2010.4

  A series of indene analogs of the H1-antihistamine (−)-R-dimethindene was evaluated for selectivity in the search for potentially improved sedative-hypnotics. Variation of the 6-substitutent in the indene core in combination with a pendant electron rich heterocycle led to the identification of several potent H1-antihistamines with desirable selectivity over CYP enzymes, the M1 muscarinic receptor and

  在寻找潜在改善的镇静催眠药的过程中，评估了H 1-抗组胺（-）- R-二甲基茚的一系列茚类似物的选择性。茚核心中6位取代基与丰富的电子侧链结合的变化导致鉴定出几种有效的H 1-抗组胺药，它们对CYP酶，M 1毒蕈碱受体和hERG通道具有理想的选择性。这些化合物是进一步ADME分析和体内评估的候选药物。
• Radler; Wermeille; Blaschke, Arzneimittel-Forschung/Drug Research, 1995, vol. 45, # 10, p. 1086 - 1092
  作者：Radler、Wermeille、Blaschke

  DOI：——

  日期：——