2-[3-[1-[2-(4-Methoxyphenyl)ethenyl]-2,5-dioxoimidazolidin-4-ylidene]propyl]guanidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2-[3-[1-[2-(4-Methoxyphenyl)ethenyl]-2,5-dioxoimidazolidin-4-ylidene]propyl]guanidine
• 英文别名: 2-[3-[1-[2-(4-methoxyphenyl)ethenyl]-2,5-dioxoimidazolidin-4-ylidene]propyl]guanidine
• 化学式: C₁₆H₁₉N₅O₃
• 分子量: 329.359
• InChiKey: OIBAUBRNXIHMBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[3-[1-[2-(4-Methoxyphenyl)ethenyl]-2,5-dioxoimidazolidin-4-ylidene]propyl]guanidine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以46%的产率得到C₁₅H₁₇N₅O₃
  参考文献：
  名称：

  Identification of the hydantoin alkaloids parazoanthines as novel CXCR4 antagonists by computational and in vitro functional characterization

  摘要：

  CXCR4 chemokine receptor represents an attractive pharmacological target due to its key role in cancer metastasis and inflammatory diseases. Starting from our previously-developed pharmacophoric model, we applied a combined computational and experimental approach that led to the identification of the hydantoin alkaloids parazoanthines, isolated from the Mediterranean Sea anemone Parazoanthus axinellae, as novel CXCR4 antagonists. Parazoanthine analogues were then synthesized to evaluate the contribution of functional groups to the overall activity. Within the panel of synthesized natural and non-natural parazoanthines, parazoanthine-B was identified as the most potent CXCR4 antagonist with an IC₅₀ value of 9.3 nM, even though all the investigated compounds were able to antagonize in vitro the down-stream effects of CXC12, albeit with variable potency and efficacy. The results of our study strongly support this class of small molecules as potent CXCR4 antagonists in tumoral pathologies characterized by an overexpression of this receptor. Furthermore, their structure-activity relationships allowed the optimization of our pharmacophoric model, useful for large-scale in silico screening.

  DOI：

  10.1016/j.bioorg.2020.104337
• 作为产物：
  描述：

  对甲氧基苯乙酮 在 sodium tetrahydroborate 、 乙醇 、 四丁基溴化铵 、 溴 、 potassium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.0h， 生成 2-[3-[1-[2-(4-Methoxyphenyl)ethenyl]-2,5-dioxoimidazolidin-4-ylidene]propyl]guanidine
  参考文献：
  名称：

  Identification of the hydantoin alkaloids parazoanthines as novel CXCR4 antagonists by computational and in vitro functional characterization

  摘要：

  CXCR4 chemokine receptor represents an attractive pharmacological target due to its key role in cancer metastasis and inflammatory diseases. Starting from our previously-developed pharmacophoric model, we applied a combined computational and experimental approach that led to the identification of the hydantoin alkaloids parazoanthines, isolated from the Mediterranean Sea anemone Parazoanthus axinellae, as novel CXCR4 antagonists. Parazoanthine analogues were then synthesized to evaluate the contribution of functional groups to the overall activity. Within the panel of synthesized natural and non-natural parazoanthines, parazoanthine-B was identified as the most potent CXCR4 antagonist with an IC₅₀ value of 9.3 nM, even though all the investigated compounds were able to antagonize in vitro the down-stream effects of CXC12, albeit with variable potency and efficacy. The results of our study strongly support this class of small molecules as potent CXCR4 antagonists in tumoral pathologies characterized by an overexpression of this receptor. Furthermore, their structure-activity relationships allowed the optimization of our pharmacophoric model, useful for large-scale in silico screening.

  DOI：

  10.1016/j.bioorg.2020.104337

文献信息

• Identification of the hydantoin alkaloids parazoanthines as novel CXCR4 antagonists by computational and in vitro functional characterization
  作者：Rosa Maria Vitale、Stefano Thellung、Francesco Tinto、Agnese Solari、Monica Gatti、Genoveffa Nuzzo、Efstathia Ioannou、Vassilios Roussis、Maria Letizia Ciavatta、Emiliano Manzo、Tullio Florio、Pietro Amodeo

  DOI：10.1016/j.bioorg.2020.104337

  日期：2020.12

  CXCR4 chemokine receptor represents an attractive pharmacological target due to its key role in cancer metastasis and inflammatory diseases. Starting from our previously-developed pharmacophoric model, we applied a combined computational and experimental approach that led to the identification of the hydantoin alkaloids parazoanthines, isolated from the Mediterranean Sea anemone Parazoanthus axinellae, as novel CXCR4 antagonists. Parazoanthine analogues were then synthesized to evaluate the contribution of functional groups to the overall activity. Within the panel of synthesized natural and non-natural parazoanthines, parazoanthine-B was identified as the most potent CXCR4 antagonist with an IC₅₀ value of 9.3 nM, even though all the investigated compounds were able to antagonize in vitro the down-stream effects of CXC12, albeit with variable potency and efficacy. The results of our study strongly support this class of small molecules as potent CXCR4 antagonists in tumoral pathologies characterized by an overexpression of this receptor. Furthermore, their structure-activity relationships allowed the optimization of our pharmacophoric model, useful for large-scale in silico screening.