8-{4-[2-(3,4-Difluoro-phenyl)-ethyl]-piperazin-1-yl}-2,9-dimethyl-9H-1,5,7,9-tetraaza-fluorene-4-carbonitrile | 676602-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 8-{4-[2-(3,4-Difluoro-phenyl)-ethyl]-piperazin-1-yl}-2,9-dimethyl-9H-1,5,7,9-tetraaza-fluorene-4-carbonitrile
• 英文别名: 6-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-8,11-dimethyl-3,5,8,10-tetrazatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene-13-carbonitrile
• CAS: 676602-36-1
• 化学式: C₂₄H₂₃F₂N₇
• 分子量: 447.49
• InChiKey: MECOLUCWZLXWNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-{4-[2-(3,4-Difluoro-phenyl)-ethyl]-piperazin-1-yl}-2,9-dimethyl-9H-1,5,7,9-tetraaza-fluorene-4-carbonitrile 在 sodium hydroxide 、 双氧水 作用下， 以 甲醇 为溶剂， 反应 72.0h， 生成 8-{4-[2-(3,4-difluoro-phenyl)-ethyl]-piperazin-1-yl}-2,9-dimethyl-9H-1,5,7,9-tetraaza-fluorene-4-carboxylic acid amide
  参考文献：
  名称：

  Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance

  摘要：

  In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.

  DOI：

  10.1021/jm0310129
• 作为产物：
  描述：

  2-氯-6-甲基吡啶-3,4-二腈 在 氨 、 三乙胺盐酸盐 、 potassium carbonate 、 caesium carbonate 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 8-{4-[2-(3,4-Difluoro-phenyl)-ethyl]-piperazin-1-yl}-2,9-dimethyl-9H-1,5,7,9-tetraaza-fluorene-4-carbonitrile
  参考文献：
  名称：

  Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance

  摘要：

  In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.

  DOI：

  10.1021/jm0310129