1-(([1,1'-biphenyl]-4-ylmethyl)amino)-3-(3-(phenylamino)phenoxy)propan-2-ol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(([1,1'-biphenyl]-4-ylmethyl)amino)-3-(3-(phenylamino)phenoxy)propan-2-ol
• 英文别名: Anti-melanoma agent 1；1-(3-anilinophenoxy)-3-[(4-phenylphenyl)methylamino]propan-2-ol
• 化学式: C₂₈H₂₈N₂O₂
• 分子量: 424.543
• InChiKey: OOXIDWAKDUZBSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.63
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  53.52
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  间羟基二苯胺 在 sodium hydroxide 作用下， 以 水 、 二甲基亚砜 、 异丙醇 为溶剂， 反应 7.33h， 生成 1-(([1,1'-biphenyl]-4-ylmethyl)amino)-3-(3-(phenylamino)phenoxy)propan-2-ol
  参考文献：
  名称：

  Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents

  摘要：

  Malignant melanoma (MM) presents as the highest morbidity and mortality type in skin cancer. Herein, inspired by the previously reported anti-melanoma effect of propranolol, a widely applied beta adrenergic receptor antagonist as cardiovascular drug, we set out to exploit its potential as anti-melanoma therapy based on the drug repurposing strategy. Structural optimization of propranolol yielded 5m, which exhibits dramatically improved potency on human melanoma cell growth (1.98-3.70 mu M), compared to propranolol (59.5-75.8 mu M). Further investigation demonstrated that 5m could inhibit colony formation of melanoma cell line (completely abolished at 2 mu M for 5m, partially inhibited at 50 mu M for propranolol), induce cell apoptosis and cell cycle arrest in the G(2)/M phase (both observed at 1 mu M). Preliminary mechanism study indicated that 5m could disrupt the cellular microtubule network, which suggested tubulin as a potential target. Docking study provided a structural insight into the interaction between 5m and tubulin. In summary, our study presents a drug repurposing case that redirects a cardiovascular agent to an anti-melanoma agent.

  DOI：

  10.1016/j.bmc.2020.115404

文献信息

• Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents
  作者：Qi Chang、Jing Long、Liqing Hu、Zhuo Chen、Qianbin Li、Gaoyun Hu

  DOI：10.1016/j.bmc.2020.115404

  日期：2020.5

  Malignant melanoma (MM) presents as the highest morbidity and mortality type in skin cancer. Herein, inspired by the previously reported anti-melanoma effect of propranolol, a widely applied beta adrenergic receptor antagonist as cardiovascular drug, we set out to exploit its potential as anti-melanoma therapy based on the drug repurposing strategy. Structural optimization of propranolol yielded 5m, which exhibits dramatically improved potency on human melanoma cell growth (1.98-3.70 mu M), compared to propranolol (59.5-75.8 mu M). Further investigation demonstrated that 5m could inhibit colony formation of melanoma cell line (completely abolished at 2 mu M for 5m, partially inhibited at 50 mu M for propranolol), induce cell apoptosis and cell cycle arrest in the G(2)/M phase (both observed at 1 mu M). Preliminary mechanism study indicated that 5m could disrupt the cellular microtubule network, which suggested tubulin as a potential target. Docking study provided a structural insight into the interaction between 5m and tubulin. In summary, our study presents a drug repurposing case that redirects a cardiovascular agent to an anti-melanoma agent.