2-Trifluormethyl-10-(3-pyrrolidino-propyl)-phenothiazin | 3793-54-2

• 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: 2-Trifluormethyl-10-(3-pyrrolidino-propyl)-phenothiazin
• 英文别名: 10-(3-pyrrolidin-1-yl-propyl)-2-trifluoromethyl-10H-phenothiazine；10-(3-pyrrolidino-propyl)-2-trifluoromethyl-phenothiazine；10-(3-Pyrrolidino-propyl)-2-trifluormethyl-phenothiazin；10-(3-Pyrrolidin-1-ylpropyl)-2-(trifluoromethyl)phenothiazine
• CAS: 3793-54-2
• 化学式: C₂₀H₂₁F₃N₂S
• 分子量: 378.461
• InChiKey: DEIFGONWDGWANH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  31.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-三氟甲基吩噻嗪 在 potassium phosphate 、 sodium hydride 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-Trifluormethyl-10-(3-pyrrolidino-propyl)-phenothiazin
  参考文献：
  名称：

  Antifungal Phenothiazines: Optimization, Characterization of Mechanism, and Modulation of Neuroreceptor Activity

  摘要：

  New classes of antifungal drugs are an urgent unmet clinical need. One approach to the challenge of developing new antifungal drugs is to optimize the antifungal properties of currently used drugs with favorable pharmacologic properties, so-called drug or scaffold repurposing. New therapies for cryptococcal meningitis are particularly important given its worldwide burden of disease and limited therapeutic options. We report the first systematic structure-activity study of the anticryptococcal properties of the phenothiazines. We also show that the antifungal activity of the phenothiazine scaffold correlates well with its calmodulin antagonism properties and, thereby, provides the first insights into the mechanism of its antifungal properties. Guided by this mechanism, we have generated improved trifluoperazine derivatives with increased anticryptococcal activity and, importantly, reduced affinity for receptors that modulate undesired neurological effects. Taken together, these data suggest that phenothiazines represent a potentially useful scaffold for further optimization in the search for new antifungal drugs.

  DOI：

  10.1021/acsinfecdis.7b00157

文献信息

• Antifungal Phenothiazines: Optimization, Characterization of Mechanism, and Modulation of Neuroreceptor Activity
  作者：Marhiah C. Montoya、Louis DiDone、Richard F. Heier、Marvin J. Meyers、Damian J. Krysan

  DOI：10.1021/acsinfecdis.7b00157

  日期：2018.4.13

  New classes of antifungal drugs are an urgent unmet clinical need. One approach to the challenge of developing new antifungal drugs is to optimize the antifungal properties of currently used drugs with favorable pharmacologic properties, so-called drug or scaffold repurposing. New therapies for cryptococcal meningitis are particularly important given its worldwide burden of disease and limited therapeutic options. We report the first systematic structure-activity study of the anticryptococcal properties of the phenothiazines. We also show that the antifungal activity of the phenothiazine scaffold correlates well with its calmodulin antagonism properties and, thereby, provides the first insights into the mechanism of its antifungal properties. Guided by this mechanism, we have generated improved trifluoperazine derivatives with increased anticryptococcal activity and, importantly, reduced affinity for receptors that modulate undesired neurological effects. Taken together, these data suggest that phenothiazines represent a potentially useful scaffold for further optimization in the search for new antifungal drugs.