N-methyl-3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)-propan-1-amine | 1479-81-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: N-methyl-3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)-propan-1-amine
• 英文别名: N-methyl-3-[2-(trifluoromethyl)-10-phenothiazinyl]-1-propanamine；N-methyl-3-[2-(trifluoromethyl)phenothiazin-10-yl]propan-1-amine
• CAS: 1479-81-8
• 化学式: C₁₇H₁₇F₃N₂S
• 分子量: 338.397
• InChiKey: OJLFFESELHQPKS-UHFFFAOYSA-N

物化性质

• 沸点：
  432.9±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲醛-13C 、 N-methyl-3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)-propan-1-amine 在 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以83%的产率得到N-([13C]methyl)-N-methyl-2-(trifluoromethyl)-10H-phenothiazine-10-propanamine
  参考文献：
  名称：

  Synthesis of [N-13CH3] drugs (chlorpromazine, triflupromazine and promazine)

  摘要：

  These [N-(CH3)-C-13] containing drugs (chlorpromazine, triflupromazine and promazine) have been synthesized by means of a two-step demethylation/methylation procedure.

  DOI：

  10.1002/1099-1344(200008)43:9<865::aid-jlcr370>3.0.co;2-e
• 作为产物：
  描述：

  10-(N-acetyl-3-aminopropyl)-2-trifluoromethyl-10H-phenothiazine 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.42h， 生成 N-methyl-3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)-propan-1-amine
  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

• [EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
  申请人：CAMP4 THERAPEUTICS CORP

  公开号：WO2019195789A1

  公开（公告）日：2019-10-10

  The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).

  本发明提供了吩噻嗪化合物，其制备方法，包含该化合物的药物组合物，以及在治疗各种疾病或症状中使用该化合物或组合物，例如核糖体紊乱和核糖体病，例如钻石-布莱克范贫血（DBA）。
• PHENOTHIAZINE DERIVATIVES AND USES THEREOF
  申请人：Camp4 Therapeutics Corporation

  公开号：US20210061837A1

  公开（公告）日：2021-03-04

  The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).
• 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.
• Synthesis of [N-13CH3] drugs (chlorpromazine, triflupromazine and promazine)
  作者：Keisuke Kitamura、Kazuyoshi Fujitani、Keiko Takahashi、Yoshimi Tanaka、Syou Hirako、Chie Kotani、Tomoko Hashimoto、Shigehiko Takegami

  DOI：10.1002/1099-1344(200008)43:9<865::aid-jlcr370>3.0.co;2-e

  日期：2000.8

  These [N-(CH3)-C-13] containing drugs (chlorpromazine, triflupromazine and promazine) have been synthesized by means of a two-step demethylation/methylation procedure.