8-[5-(4-methylpiperazin-1-yl)-2-trifluoromethoxyphenylamino]-1-trityl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide | 1034615-39-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 8-[5-(4-methylpiperazin-1-yl)-2-trifluoromethoxyphenylamino]-1-trityl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 英文别名: 8-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenylamino)-1-trityl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide；8-[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)anilino]-1-trityl-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide
• CAS: 1034615-39-8
• 化学式: C₄₁H₃₇F₃N₈O₂
• 分子量: 730.792
• InChiKey: ASPGNMNPVXBVLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  54
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  8-[5-(4-methylpiperazin-1-yl)-2-trifluoromethoxyphenylamino]-1-trityl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到8-((5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  4,5-Dihydro-1H-pyrazolo[4,3-h]quinazolines as potent and selective Polo-like kinase 1 (PLK1) inhibitors

  摘要：

  A series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives was optimized as Polo-like kinase 1 inhibitors. Extensive SAR afforded a highly potent and selective PLK1 compound. The compound showed good antiproliferative activity when tested in a panel of tumor cell lines with PLK1 related mechanism of action and with good in vivo antitumor efficacy in two xenograft models after iv administration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.060
• 作为产物：
  描述：

  5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)aniline 、 8-iodo-1-trityl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 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， 反应 20.0h， 以30%的产率得到8-[5-(4-methylpiperazin-1-yl)-2-trifluoromethoxyphenylamino]-1-trityl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  4,5-Dihydro-1H-pyrazolo[4,3-h]quinazolines as potent and selective Polo-like kinase 1 (PLK1) inhibitors

  摘要：

  A series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives was optimized as Polo-like kinase 1 inhibitors. Extensive SAR afforded a highly potent and selective PLK1 compound. The compound showed good antiproliferative activity when tested in a panel of tumor cell lines with PLK1 related mechanism of action and with good in vivo antitumor efficacy in two xenograft models after iv administration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.060

文献信息

• 4,5-Dihydro-1H-pyrazolo[4,3-h]quinazolines as potent and selective Polo-like kinase 1 (PLK1) inhibitors
  作者：Italo Beria、Barbara Valsasina、Maria Gabriella Brasca、Walter Ceccarelli、Maristella Colombo、Sabrina Cribioli、Gabriele Fachin、Ronald D. Ferguson、Francesco Fiorentini、Laura M. Gianellini、Maria L. Giorgini、Jurgen K. Moll、Helena Posteri、Daniele Pezzetta、Fulvia Roletto、Francesco Sola、Dania Tesei、Michele Caruso

  DOI：10.1016/j.bmcl.2010.09.060

  日期：2010.11

  A series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives was optimized as Polo-like kinase 1 inhibitors. Extensive SAR afforded a highly potent and selective PLK1 compound. The compound showed good antiproliferative activity when tested in a panel of tumor cell lines with PLK1 related mechanism of action and with good in vivo antitumor efficacy in two xenograft models after iv administration. (C) 2010 Elsevier Ltd. All rights reserved.