(3-甲基氨基丙基)-5H-二苯并[b,f]氮杂卓 | 2010-13-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: (3-甲基氨基丙基)-5H-二苯并[b,f]氮杂卓
• 中文别名: 5-[3-（甲基氨基）丙基]-5H-二苯并[b，f]a庚因-d3
• 英文名称: 5-(3-methylaminopropyl)-5H-dibenzazepine
• 英文别名: 3-(5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine；protripyline；(3-Methylaminopropyl)-5H-dibenz[b,f]azepine；3-benzo[b][1]benzazepin-11-yl-N-methylpropan-1-amine
• CAS: 2010-13-1
• 化学式: C₁₈H₂₀N₂
• 分子量: 264.37
• InChiKey: QRLPHVTVHACZGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-(3-(5H-dibenzo[b,f]azepin-5-yl)propyl)acetamide 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.42h， 生成 (3-甲基氨基丙基)-5H-二苯并[b,f]氮杂卓
  参考文献：
  名称：

  A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential

  摘要：

  Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold. Thus, we designed a focused-chemical library of 36 entries aimed at exploring the structural requirements for efficient neuroprotective/neuroregenerative cellular activity, without the manifestation of toxicity. To this aim, we developed a synthetic protocol, which overcame the limited applicability of previously reported procedures. Next, we evaluated the synthesized compounds through a phenotypic screening pipeline, based on primary neuronal systems. Phenothiazine 2Bc showed improved neuroregenerative and neuroprotective properties with respect to reference drug desipramine (2Aa). Importantly, we have also shown that 2Bc outperformed currently available drugs in cell models of Alzheimer's and Parkinson's diseases and attenuates microglial activation by reducing iNOS expression.

  DOI：

  10.1021/acschemneuro.8b00242

文献信息

• US4249003A
  申请人：——

  公开号：US4249003A

  公开（公告）日：1981-02-03
• [EN] COMPOUNDS THAT INHIBIT CHOLINESTERASE<br/>[FR] COMPOSÉS INHIBITEURS DE CHOLINESTÉRASE
  申请人：COLUCID PHARMACEUTICALS INC

  公开号：WO2008097546A2

  公开（公告）日：2008-08-14

  [EN] Compounds that inhibit cholinesterase activity and, upon hydrolysis release a pharmacologically active agent. The pharmacologically active agent obtained by hydrolysis of the compound can treat, for example, a nervous system condition, a cholinergic deficiency and conditions or diseases associated with a deficiency in a pharmacologically active agent, such as acetylcholine.
  [FR] L'invention concerne des composés qui inhibent une activité de la cholinestérase et, après hydrolyse, libèrent un agent pharmacologiquement actif. L'agent pharmacologiquement actif obtenu par une hydrolyse du composé peut traiter, par exemple, une affection du système nerveux, une déficience cholinergique et des états ou maladies associés à une carence en un agent pharmacologiquement actif, comme l'acétylcholine.
• A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential
  作者：Elisa Uliassi、Luis Emiliano Peña-Altamira、Aixa V. Morales、Francesca Massenzio、Sabrina Petralla、Michele Rossi、Marinella Roberti、Loreto Martinez Gonzalez、Ana Martinez、Barbara Monti、Maria Laura Bolognesi

  DOI：10.1021/acschemneuro.8b00242

  日期：2019.1.16

  Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold. Thus, we designed a focused-chemical library of 36 entries aimed at exploring the structural requirements for efficient neuroprotective/neuroregenerative cellular activity, without the manifestation of toxicity. To this aim, we developed a synthetic protocol, which overcame the limited applicability of previously reported procedures. Next, we evaluated the synthesized compounds through a phenotypic screening pipeline, based on primary neuronal systems. Phenothiazine 2Bc showed improved neuroregenerative and neuroprotective properties with respect to reference drug desipramine (2Aa). Importantly, we have also shown that 2Bc outperformed currently available drugs in cell models of Alzheimer's and Parkinson's diseases and attenuates microglial activation by reducing iNOS expression.