(+/-)-2-[7-(4-bromophenyl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenol

• 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)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenol
• 英文别名: 2-[7-(4-bromophenyl)-1,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenol
• 化学式: C₁₇H₁₃BrN₄O
• 分子量: 369.22
• InChiKey: HFGLOSSKYVCKOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-2-[7-(4-bromophenyl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenol 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.67h， 生成
  参考文献：
  名称：

  Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors

  摘要：

  Human murine double minute 2 (MDM2) is a negative regulator of p53, which plays an important role in cell cycle and apoptosis. We report several optimizations to the synthesis of the chromenotriazolopyrimidine series of MDM2-p53 protein-protein interaction inhibitors. Additionally, the in vitro and in vivo stability, pharmacokinetic properties and solubility were improved through N-substitution. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.027
• 作为产物：
  描述：

  对溴苯甲醛 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 16.5h， 生成 (+/-)-2-[7-(4-bromophenyl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenol
  参考文献：
  名称：

  Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors

  摘要：

  Human murine double minute 2 (MDM2) is a negative regulator of p53, which plays an important role in cell cycle and apoptosis. We report several optimizations to the synthesis of the chromenotriazolopyrimidine series of MDM2-p53 protein-protein interaction inhibitors. Additionally, the in vitro and in vivo stability, pharmacokinetic properties and solubility were improved through N-substitution. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.027

文献信息

• Discovery and Optimization of Chromenotriazolopyrimidines as Potent Inhibitors of the Mouse Double Minute 2−Tumor Protein 53 Protein−Protein Interaction
  作者：John G. Allen、Matthew P. Bourbeau、G. Erich Wohlhieter、Michael D. Bartberger、Klaus Michelsen、Randall Hungate、Robert C. Gadwood、Rick D. Gaston、Bruce Evans、Larry W. Mann、Michael E. Matison、Stephen Schneider、Xin Huang、Dongyin Yu、Paul S. Andrews、Andreas Reichelt、Alexander M. Long、Peter Yakowec、Evelyn Y. Yang、Tani Ann Lee、Jonathan D. Oliner

  DOI：10.1021/jm900681h

  日期：2009.11.26

  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.
• Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors
  作者：Hilary P. Beck、Michael DeGraffenreid、Brian Fox、John G. Allen、Yosup Rew、Stephen Schneider、Anne Y. Saiki、Dongyin Yu、Jonathan D. Oliner、Kevin Salyers、Qiuping Ye、Steven Olson

  DOI：10.1016/j.bmcl.2010.11.027

  日期：2011.5

  Human murine double minute 2 (MDM2) is a negative regulator of p53, which plays an important role in cell cycle and apoptosis. We report several optimizations to the synthesis of the chromenotriazolopyrimidine series of MDM2-p53 protein-protein interaction inhibitors. Additionally, the in vitro and in vivo stability, pharmacokinetic properties and solubility were improved through N-substitution. (C) 2010 Elsevier Ltd. All rights reserved.