8-(5-((2-(diethylamino)ethyl)(methyl)amino)-2-(trifluoromethoxy)phenylamino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide | 1034616-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-(5-((2-(diethylamino)ethyl)(methyl)amino)-2-(trifluoromethoxy)phenylamino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 英文别名: 8-[5-[2-(diethylamino)ethyl-methylamino]-2-(trifluoromethoxy)anilino]-1-methyl-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide
• CAS: 1034616-34-6
• 化学式: C₂₅H₃₁F₃N₈O₂
• 分子量: 532.569
• InChiKey: PCGFAESANBCIRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-三氟甲氧基-5-溴苯胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 lithium hexamethyldisilazane 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-(5-((2-(diethylamino)ethyl)(methyl)amino)-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

文献信息

• NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor
  作者：Italo Beria、Roberto T. Bossi、Maria Gabriella Brasca、Michele Caruso、Walter Ceccarelli、Gabriele Fachin、Marina Fasolini、Barbara Forte、Francesco Fiorentini、Enrico Pesenti、Daniele Pezzetta、Helena Posteri、Alessandra Scolaro、Stefania Re Depaolini、Barbara Valsasina

  DOI：10.1016/j.bmcl.2011.03.054

  日期：2011.5

  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.