10-{3-[4-(2-pyrimidyl)piperazin-1-yl]-2-hydroxypropyl}-2-(trifluoromethyl)phenothiazine | 1552360-84-5

• 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-{3-[4-(2-pyrimidyl)piperazin-1-yl]-2-hydroxypropyl}-2-(trifluoromethyl)phenothiazine
• 英文别名: 1-(4-Pyrimidin-2-ylpiperazin-1-yl)-3-[2-(trifluoromethyl)phenothiazin-10-yl]propan-2-ol；1-(4-pyrimidin-2-ylpiperazin-1-yl)-3-[2-(trifluoromethyl)phenothiazin-10-yl]propan-2-ol
• CAS: 1552360-84-5
• 化学式: C₂₄H₂₄F₃N₅OS
• 分子量: 487.549
• InChiKey: UJHLVRCDGHDZAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

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

  Phase Separation in Phosphatidylcholine Membrane Caused by the Presence of a Pyrimidine Analogue of Fluphenazine with High Anti-Multidrug-Resistance Activity

  摘要：

  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.

  DOI：

  10.1021/jp410882r
• 作为产物：
  描述：

  1-(2-嘧啶基)哌嗪 、 10-(2,3-epoxypropyl)-2-trifluoromethylphenothiazine 以 乙醇 为溶剂， 反应 6.0h， 生成 10-{3-[4-(2-pyrimidyl)piperazin-1-yl]-2-hydroxypropyl}-2-(trifluoromethyl)phenothiazine
  参考文献：
  名称：

  Phase Separation in Phosphatidylcholine Membrane Caused by the Presence of a Pyrimidine Analogue of Fluphenazine with High Anti-Multidrug-Resistance Activity

  摘要：

  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.

  DOI：

  10.1021/jp410882r

文献信息

• 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.