(+/-)-2-[7-(4-bromophenyl)-4-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-4-chlorophenol | 1196203-50-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: (+/-)-2-[7-(4-bromophenyl)-4-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-4-chlorophenol
• CAS: 1196203-50-5
• 化学式: C₁₈H₁₄BrClN₄O
• 分子量: 417.692
• InChiKey: KYDIQEWUOXSMDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  54.18
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (+/-)-2-[7-(4-bromophenyl)-4-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-4-chlorophenol 、 4-溴苯甲醛二甲缩醛 在 三氟乙酸 、 samarium(III) trifluoromethanesulfonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以7%的产率得到(+/-)-syn-6,7-bis(4-bromophenyl)-2-chloro-12-methyl-7,12-dihydro-6H-chromeno[4,3-d][1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Discovery and Optimization of Chromenotriazolopyrimidines as Potent Inhibitors of the Mouse Double Minute 2−Tumor Protein 53 Protein−Protein Interaction

  摘要：

  Tumor protein 53 (p53) is a critical regulator of cell cycle and apoptosis that is frequently disabled in human tumors. In many tumor types, p53 is deleted or mutated, but in others p53 is inactivated by overexpression or amplification of its negative regulator mouse double minute 2 (MDM2). A high-throughput screening effort identified 6,7-bis(4-bromophenyl)-7,12-dihydro-6H-chromeno[4,3-d]-[1,2,4]triazolo[1,5-a]pyrimidine as a potent inhibitor of the MDM2-p53 protein-protein interaction. This screening hit was found to be chemically unstable and difficult to handle due to poor DMSO solubility. Co-crystallization with the target protein helped to direct further optimization and provided a tractable lead series of novel MDM2-p53 inhibitors. In cellular assays, these compounds were shown to upregulate p53 protein levels and p53 signaling and to cause p53-dependent inhibition of proliferation and apoptosis.

  DOI：

  10.1021/jm900681h
• 作为产物：
  描述：

  在 水 、 caesium carbonate 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 1.0h， 生成 (+/-)-2-[7-(4-bromophenyl)-4-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]-4-chlorophenol
  参考文献：
  名称：

  Discovery and Optimization of Chromenotriazolopyrimidines as Potent Inhibitors of the Mouse Double Minute 2−Tumor Protein 53 Protein−Protein Interaction

  摘要：

  Tumor protein 53 (p53) is a critical regulator of cell cycle and apoptosis that is frequently disabled in human tumors. In many tumor types, p53 is deleted or mutated, but in others p53 is inactivated by overexpression or amplification of its negative regulator mouse double minute 2 (MDM2). A high-throughput screening effort identified 6,7-bis(4-bromophenyl)-7,12-dihydro-6H-chromeno[4,3-d]-[1,2,4]triazolo[1,5-a]pyrimidine as a potent inhibitor of the MDM2-p53 protein-protein interaction. This screening hit was found to be chemically unstable and difficult to handle due to poor DMSO solubility. Co-crystallization with the target protein helped to direct further optimization and provided a tractable lead series of novel MDM2-p53 inhibitors. In cellular assays, these compounds were shown to upregulate p53 protein levels and p53 signaling and to cause p53-dependent inhibition of proliferation and apoptosis.

  DOI：

  10.1021/jm900681h