3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)propan-1-amine | 2095-14-9

• 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: 3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)propan-1-amine
• 英文别名: 3-[2-(trifluoromethyl)phenothiazin-10-yl]propan-1-amine
• CAS: 2095-14-9
• 化学式: C₁₆H₁₅F₃N₂S
• 分子量: 324.37
• InChiKey: YCSUPUAUBAFLBJ-UHFFFAOYSA-N

物化性质

• 沸点：
  176-178 °C(Press: 0.6 Torr)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)propan-1-amine 在 甲酸 作用下， 以 水 为溶剂， 反应 8.0h， 以48%的产率得到三氟丙嗪
  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
• 作为产物：
  描述：

  10-(3-氯丙基)-2-(三氟甲基)-10H-吩噻嗪 在 一水合肼 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 23.0h， 生成 3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)propan-1-amine
  参考文献：
  名称：

  [EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS

  摘要：

  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）。

  公开号：

  WO2019195789A1

文献信息

• Phenothiazine-Tacrine Heterodimers: Pursuing Multitarget Directed Approach in Alzheimer’s Disease
  作者：Lukas Gorecki、Elisa Uliassi、Manuela Bartolini、Jana Janockova、Martina Hrabinova、Vendula Hepnarova、Lukas Prchal、Lubica Muckova、Jaroslav Pejchal、Jana Z. Karasova、Eva Mezeiova、Marketa Benkova、Tereza Kobrlova、Ondrej Soukup、Sabrina Petralla、Barbara Monti、Jan Korabecny、Maria Laura Bolognesi

  DOI：10.1021/acschemneuro.1c00184

  日期：2021.5.5

  an effective therapy is urgently needed. We followed the so-called “multitarget directed ligand” approach and designed 36 novel tacrine-phenothiazine heterodimers which were in vitro evaluated for their anticholinesterase properties. The assessment of the structure–activity relationships of such derivatives highlighted compound 1dC as a potent and selective acetylcholinesterase inhibitor with IC50

  自2002年以来，没有针对阿尔茨海默氏病的临床候选药物上市。因此，迫切需要一种有效的治疗方法。我们遵循所谓的“多靶标定向配体”方法，设计了36种新型他克林-吩噻嗪异二聚体，并对其体外抗胆碱酯酶特性进行了评估。对这类衍生物的构效关系的评估突出了化合物1dC作为有效的选择性乙酰胆碱酯酶抑制剂，IC 50 = 8 nM，1aA作为有效的丁酰胆碱酯酶抑制剂，IC 50 = 15 nM。选定的杂种，即1aC，1bC，1cC，1dC和2dC表现出对τ （306-336）肽聚集的显着抑制活性，抑制百分比范围为50.5至62.1％。同样，1dC和2dC具有抑制自诱导的Aβ1–42聚集的显着能力。尽管如此，体外研究显示对HepG2细胞和小脑颗粒神经元具有细胞毒性。当以14 mg / kg（ip）对小鼠施用1dC时，未观察到病理生理异常。如体外和体内模型所示，1dC还能够渗透到CNS中。最大大脑浓度接近IC乙
• Polymeric Compounds And Methods Of Making And Using The Same
  申请人：Fan Xiaodong

  公开号：US20140308317A1

  公开（公告）日：2014-10-16

  The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, malaria, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; killing or inhibiting the growth of a Plasmodium species; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin/low molecular weight heparin derivative.

  本公开提供化合物或其药学上可接受的盐，用于抑制微生物的生长；治疗患有微生物感染，疟疾，口腔炎，眼部感染，耳部感染，癌症或结核分枝杆菌感染的哺乳动物；杀死或抑制疟原虫的生长；抑制结核分枝杆菌的生长；调节哺乳动物的免疫反应；或拮抗非分散肝素，低分子量肝素或肝素/低分子量肝素衍生物。
• THERAPEUTIC COMPOSITION AND TREATMENT METHOD FOR AMYLOID NEUROLOGICAL DISEASES
  申请人：Amyloid Solution Inc.

  公开号：EP3888655A1

  公开（公告）日：2021-10-06

  Provided are a novel pharmaceutical composition and method for the inhibition and/or degradation of amyloid aggregation, and/or degradation of Tau, and/or inhibition of Tau phosphorylation, and/or the prevention and/or treatment of neurodegenerative brain disease.

  本文提供了一种新型药物组合物和方法，用于抑制和/或降解淀粉样蛋白聚集，和/或降解Tau，和/或抑制Tau磷酸化，和/或预防和/或治疗神经退行性脑病。
• Potential Antihypertensive Agents. Some Guanidine Derivatives
  作者：D. I. Barron、P. M. G. Bavin、G. J. Durant、I. L. Natoff、R. G. W. Spickett、D. K. Vallance

  DOI：10.1021/jm00342a017

  日期：1963.11
• Motohashi, Noboru; Kawase, Masami; Molnar, Joseph, Arzneimittel-Forschung/Drug Research, 2003, vol. 53, # 8, p. 590 - 599
  作者：Motohashi, Noboru、Kawase, Masami、Molnar, Joseph、Ferenczy, Lajos、Wesolowska, Olga、Hendrich, Andrzej B.、Bobrowska-Haegerstrand, Malgorzata、Haegerstrand, Henry、Michalak, Krystyna

  DOI：——

  日期：——