| 500144-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• CAS: 500144-34-3
• 化学式: C₂₃H₁₉Br₂N₃O₃
• 分子量: 545.23
• InChiKey: GYBOOIGZHWCERQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.43
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  4-溴苯乙酮 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 15.25h， 生成
  参考文献：
  名称：

  Discovery, Synthesis, and Biological Evaluation of Orally Active Pyrrolidone Derivatives as Novel Inhibitors of p53–MDM2 Protein–Protein Interaction

  摘要：

  The p53-MDM2 interaction has been proved to,, be a valuable target, to develop effective antitumor agents. Novel p53-MDM2 inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. The nanomolar inhibitor 5 possessed good p53-MDM2 inhibitory activity (K-i = 780 nM) due to its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led to. the discovery of a number of highly potent pyrrolidone derivative's with improved p537-MDM2 inhibitory activity and in vitro antiproliferative potency. Compounds 41 (K-i = 260.0 nM) and 60a (K-i = 150.0 nM) showed good and selective activity against tumor cells with deleted p53. In addition, these two Compounds also :effectively inhibited the tumor growth in the A549 xenograft model: Interestingly, compound 41 was proved to be a potent MDM2/MDMX dual inhibitor. The novel pyrrolidone p53-MDM2 inhibitors represent promising lead structures for the development Of novel antitumor agents.

  DOI：

  10.1021/jm300969t

文献信息

• Discovery, Synthesis, and Biological Evaluation of Orally Active Pyrrolidone Derivatives as Novel Inhibitors of p53–MDM2 Protein–Protein Interaction
  作者：Chunlin Zhuang、Zhenyuan Miao、Lingjian Zhu、Guoqiang Dong、Zizhao Guo、Shengzheng Wang、Yongqiang Zhang、Yuelin Wu、Jianzhong Yao、Chunquan Sheng、Wannian Zhang

  DOI：10.1021/jm300969t

  日期：2012.11.26

  The p53-MDM2 interaction has been proved to,, be a valuable target, to develop effective antitumor agents. Novel p53-MDM2 inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. The nanomolar inhibitor 5 possessed good p53-MDM2 inhibitory activity (K-i = 780 nM) due to its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led to. the discovery of a number of highly potent pyrrolidone derivative's with improved p537-MDM2 inhibitory activity and in vitro antiproliferative potency. Compounds 41 (K-i = 260.0 nM) and 60a (K-i = 150.0 nM) showed good and selective activity against tumor cells with deleted p53. In addition, these two Compounds also :effectively inhibited the tumor growth in the A549 xenograft model: Interestingly, compound 41 was proved to be a potent MDM2/MDMX dual inhibitor. The novel pyrrolidone p53-MDM2 inhibitors represent promising lead structures for the development Of novel antitumor agents.