4-benzoyl-5-(4-bromophenyl)-3-[(3-bromophenyl)amino]-1-[3-(1H-imidazol-1-yl)propyl]-2,5-dihydro-1H-pyrrol-2-one | 1391501-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 4-benzoyl-5-(4-bromophenyl)-3-[(3-bromophenyl)amino]-1-[3-(1H-imidazol-1-yl)propyl]-2,5-dihydro-1H-pyrrol-2-one
• 英文别名: 3-benzoyl-4-(3-bromoanilino)-2-(4-bromophenyl)-1-(3-imidazol-1-ylpropyl)-2H-pyrrol-5-one
• CAS: 1391501-80-6
• 化学式: C₂₉H₂₄Br₂N₄O₂
• 分子量: 620.343
• InChiKey: FNKZHZBNIPGIHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(3-氨基丙基)咪唑 在 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 反应 14.25h， 生成 4-benzoyl-5-(4-bromophenyl)-3-[(3-bromophenyl)amino]-1-[3-(1H-imidazol-1-yl)propyl]-2,5-dihydro-1H-pyrrol-2-one
  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

• [EN] 1,5-DIHYDROPYRROL-2-ONE DERIVATIVES AS INHIBITORS OF P53-MDM2/MDM4 PROTEIN-PROTEIN INTERACTION<br/>[FR] DÉRIVÉS DE 1,5-DIHYDROPYRROL-2-ONE COMME INHIBITEURS DE L'INTERACTION PROTÉINÉ-PROTÉINE P53-MDM2/MDM4
  申请人：ADAMED SP ZOO

  公开号：WO2015004610A1

  公开（公告）日：2015-01-15

  A compound of general formula (I), wherein Z is C and n is 1, or Z is Sand n is 0, R4 isisoxazolyl by one –(C1 -C6 -alkyl) or unsubstituted or substituted phenyl, and other substituents have the meaning as defined in the description, for use as a medicament. The compounds are inhibitors of interactions p53/Mdm2 and/or p53/Mdm4and can be useful in the treatment of immune system diseases, chronic inflammatory conditions, inflammatory and allergic skin diseases associated with proliferative diseases, cancer or viral infections.