2-amino-N-(9-(diethylamino)-5H-benzo[a]phenothiazin-5-ylidene)ethanaminium chloride | 1401719-05-8

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-amino-N-(9-(diethylamino)-5H-benzo[a]phenothiazin-5-ylidene)ethanaminium chloride
• 英文别名: [5-(2-aminoethylamino)benzo[a]phenothiazin-9-ylidene]-diethylazanium;chloride
• CAS: 1401719-05-8
• 化学式: C₂₂H₂₄N₄S*ClH
• 分子量: 412.986
• InChiKey: RDAJKAQILAPJOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.74
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  78.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl (2-(naphthalen-1-ylamino)ethyl)carbamate 、 sodium S-ethyl sulfurothioate 在 silver carbonate 作用下， 反应 0.5h， 生成 2-amino-N-(9-(diethylamino)-5H-benzo[a]phenothiazin-5-ylidene)ethanaminium chloride
  参考文献：
  名称：

  In Vitro Optimization of EtNBS-PDT against Hypoxic Tumor Environments with a Tiered, High-Content, 3D Model Optical Screening Platform

  摘要：

  Hypoxia and acidosis are widely recognized as major contributors to the development of treatment resistant cancer. For patients with disseminated metastatic lesions, such as most women with ovarian cancer (OvCa), the progression to treatment resistant disease is almost always fatal. Numerous therapeutic approaches have been developed to eliminate treatment resistant carcinoma, including novel biologic, chemo, radiation, and photodynamic therapy (PDT) regimens. Recently, PDT using the cationic photosensitizer EtNBS was found to be highly effective against therapeutically unresponsive hypoxic and acidic OvCa cellular populations in vitro. To optimize this treatment regimen, we developed a tiered, high-content, image-based screening approach utilizing a biologically relevant OvCa 3D culture model to investigate a small library of side-chain modified EtNBS derivatives. The uptake, localization, and photocytotoxicity of these compounds on both the cellular and nodular levels were observed to be largely mediated by their respective ethyl side chain chemical alterations. In particular, EtNBS and its hydroxyl-terminated derivative (EtNBS-OH) were found to have similar pharmacological parameters, such as their nodular localization patterns and uptake kinetics. Interestingly, these two molecules were found to induce dramatically different therapeutic outcomes: EtNBS was found to be more effective in killing the hypoxic, nodule core cells with superior selectivity, while EtNBS-OH was observed to trigger widespread structural degradation of nodules. This breakdown of the tumor architecture can improve the therapeutic outcome and is known to synergistically enhance the antitumor effects of front-line chemotherapeutic regimens. These results, which would not have been predicted or observed using traditional monolayer or in vivo animal screening techniques, demonstrate the powerful capabilities of 3D in vitro screening approaches for the selection and optimization of therapeutic agents for the targeted destruction of specific cellular subpopulations.

  DOI：

  10.1021/mp300262x