(R)-8-((5-(2-((benzyloxy)methyl)-4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide | 1034615-57-0

• 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: (R)-8-((5-(2-((benzyloxy)methyl)-4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• CAS: 1034615-57-0
• 化学式: C₃₁H₃₃F₃N₈O₃
• 分子量: 622.65
• InChiKey: XQCRMSDZZFNXMM-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.05
• 重原子数：
  45.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  123.66
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (R)-8-((5-(2-((benzyloxy)methyl)-4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 8-[5-((R)-2-hydroxymethyl-4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor

  摘要：

  As part of our drug discovery effort, we identified and developed 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. We now report the optimization of this class that led to the identification of NMS-P937, a potent, selective and orally available PLK1 inhibitor. Also, in order to understand the source of PLK1 selectivity, we determined the crystal structure of PLK1 with NMS-P937. The compound was active in vivo in HCT116 xenograft model after oral administration and is presently in Phase I clinical trials evaluation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.054
• 作为产物：
  描述：

  8-iodo-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 、 5-((R)-2-benzyloxymethyl-4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine 在 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-8-((5-(2-((benzyloxy)methyl)-4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor

  摘要：

  As part of our drug discovery effort, we identified and developed 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. We now report the optimization of this class that led to the identification of NMS-P937, a potent, selective and orally available PLK1 inhibitor. Also, in order to understand the source of PLK1 selectivity, we determined the crystal structure of PLK1 with NMS-P937. The compound was active in vivo in HCT116 xenograft model after oral administration and is presently in Phase I clinical trials evaluation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.054