10-(2,3-epoxypropyl)-2-trifluoromethylphenothiazine | 756876-08-1

• 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: 10-(2,3-epoxypropyl)-2-trifluoromethylphenothiazine
• 英文别名: 10-(oxiran-2-ylmethyl)-2-(trifluoromethyl)-10H-phenothiazine；(+/-)-10-(oxiran-2-ylmethyl)-2-(trifluoromethyl)-10H-phenothiazine；10-(oxiran-2-ylmethyl)-2-(trifluoromethyl)phenothiazine
• CAS: 756876-08-1
• 化学式: C₁₆H₁₂F₃NOS
• 分子量: 323.339
• InChiKey: VKHUSYMVKHRPIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  10-(2,3-epoxypropyl)-2-trifluoromethylphenothiazine 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 10-{3-[4-(N-isopropylcarbamoylmethyl)piperazin-1-yl]-2-hydroxypropyl}-2-trifluoromethylphenothiazine dihydrochloride
  参考文献：
  名称：

  Zyta, Joanna; Jaszczyszyn, Agata; Swiatek, Piotr, Acta poloniae pharmaceutica, 2014, vol. 71, # 1, p. 49 - 58

  摘要：

  DOI：
• 作为产物：
  描述：

  2-三氟甲基吩噻嗪 、 环氧溴丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以75%的产率得到10-(2,3-epoxypropyl)-2-trifluoromethylphenothiazine
  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

• Increased lipid peroxidation, apoptosis and selective cytotoxicity in colon cancer cell line LoVo and its doxorubicin-resistant subline LoVo/Dx in the presence of newly synthesized phenothiazine derivatives
  作者：Kamila Środa-Pomianek、Krystyna Michalak、Piotr Świątek、Andrzej Poła、Anna Palko-Łabuz、Olga Wesołowska

  DOI：10.1016/j.biopha.2018.06.170

  日期：2018.10

  compounds with a potent anticancer activity. Since phenothiazines are known as multidrug resistance modulators the sensitive human colorectal adenocarcinoma cell line (LoVo) and its doxorubicin-resistant, ABCB1 overexpressing, subline (LoVo/Dx) have been employed as a model system. In studied cancer cells cytotoxic effect of the phenothiazine derivatives was accompanied by apoptosis and autophagy induction

  癌细胞通常会对促凋亡信号产生抗性，从而使其不受常规治疗的侵害。由于避免了通常伴随坏死的炎症反应，使癌细胞进入凋亡途径的治疗策略是理想的。在本研究中，对吩噻嗪类（氟奋乃静和四种最近合成的衍生物）进行了研究，以鉴定具有有效抗癌活性的化合物。由于吩噻嗪被称为多药耐药性调节剂，因此已将敏感的人结肠直肠腺癌细胞系（LoVo）及其耐阿霉素，过表达的ABCB1亚系（LoVo / Dx）用作模型系统。在研究的癌细胞中，吩噻嗪衍生物的细胞毒性作用伴随着细胞凋亡和自噬诱导，以及细胞脂质过氧化作用的增加和细胞内活性氧种类的产生。分子建模表明，吩噻嗪的反应性（由其低能隙表现）而不具有亲脂性与它们的抗癌能力，促氧化剂特性和凋亡诱导能力呈正相关。另外，一些研究的化合物在抗阿霉素（LoVo / Dx）细胞中比对敏感化合物（LoVo）具有更强的细胞毒性和促凋亡作用。假设假设研究的吩噻嗪衍生物通过增加活性氧的产生来诱导凋亡性细胞死亡。
• TRICYCLIC COMPOUNDS USEFUL AS NEUROGENIC AND NEUROPROTECTIVE AGENTS
  申请人：INCEPTION 1, INC.

  公开号：US20140243313A1

  公开（公告）日：2014-08-28

  The invention disclosed herein is direct to compounds of Formula I and pharmaceutically acceptable salts thereof, which are useful in treating neurodegenerative diseases and promoting the generation or survival of neurons in the mammalian brain. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula I or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to a method of promoting the generation or survival of neurons in a patient in need thereof in neurodegenerative and related diseases.

  本发明涉及公式I化合物及其药学上可接受的盐，其在治疗神经退行性疾病和促进哺乳动物大脑中神经元的生成或存活方面有用。本发明还包括含有公式I化合物或其药学上可接受的盐的治疗有效量的药物组合物。本发明还涉及一种在神经退行性和相关疾病患者中促进神经元的生成或存活的方法。
• Tricyclic compounds useful as neurogenic and neuroprotective agents
  申请人：INCEPTION 1, INC.

  公开号：US09187439B2

  公开（公告）日：2015-11-17

  The invention disclosed herein is direct to compounds of Formula I and pharmaceutically acceptable salts thereof, which are useful in treating neurodegenerative diseases and promoting the generation or survival of neurons in the mammalian brain. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula I or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to a method of promoting the generation or survival of neurons in a patient in need thereof in neurodegenerative and related diseases.

  本发明涉及公式I化合物及其药学上可接受的盐，其在治疗神经退行性疾病和促进哺乳动物大脑中神经元的生成或存活方面具有用途。本发明还包括包含公式I化合物或其药学上可接受的盐的治疗有效量的药物组合物。本发明还涉及一种在需要神经退行性和相关疾病患者中促进神经元生成或存活的方法。
• [EN] TRICYCLIC COMPOUNDS USEFUL AS NEUROGENIC AND NEUROPROTECTIVE AGENTS<br/>[FR] COMPOSÉS TRICYCLIQUES UTILES COMME AGENTS NEUROGÈNES ET NEUROPROTECTEURS
  申请人：INCEPTION 1 INC

  公开号：WO2013043744A3

  公开（公告）日：2013-06-06
• Phase Separation in Phosphatidylcholine Membrane Caused by the Presence of a Pyrimidine Analogue of Fluphenazine with High Anti-Multidrug-Resistance Activity
  作者：Katarzyna Cieślik-Boczula、Piotr Świątek、Agata Jaszczyszyn、Patrycja Zawilska、Kazimierz Gąsiorowski、Wiesław Malinka、Gottfried Köhler

  DOI：10.1021/jp410882r

  日期：2014.4.3

  Phenothiazine compounds are known as effective inhibitors of a multidrug resistance (MDR) of tumor cells to chemotherapeutic agents. This group consists of many important substances used in human medicine such as antipsychotic drugs in the case of fluphenazine (FPh) or chlorpromazine (CPZ). Fluphenazine was on the World Health Organization (WHO) list of Essential Medicines of 2009, and its new pyrimidine analog (FPh-prm) presented in this work has been documented to have a high anti-MDR activity. In order to discover the character of alterations of the lipid bilayer structure caused by the presence of FPh-prm inside the lipid membrane, which is responsible for the essential increase of an anti-MDR activity of FPh-prm, microcalorimetric (differential scanning calorimetry), Laurdan fluorescence, P-31 nuclear magnetic resonance spectroscopy (NMR), and attenuated total reflectance Fourier transfer infrared spectroscopy (FTIR-ATR) were used for dipahnitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes mixed with a different concentration of amine analogue. It was stated that the formation of domains with different content of FPh-prm/DPPC can be a reason for the membrane-related mechanism of chemoprevention associated with the inhibition of the outward transport of anticancer drugs by the glycoprotein P (Pgp) in cancer cells by the pyrimidine analog of FPh. To our best knowledge, this report is the first to show the bilayer structure of domains formed by incomplete miscibility of fluphenazine-related compounds and phospholipid molecules. Our results provide a sound basis for the design of future modifications of anti-MDR drugs by providing very effective inhibitors of the pump activity of Pgp.