tert-butyl 4-[(4-{3-[(3-carbamoyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl)amino]-4-(trifluoromethoxy)phenyl}piperazin-1-yl)carbonyl]piperazine-1-carboxylate | 1258270-43-7

• 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: tert-butyl 4-[(4-{3-[(3-carbamoyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl)amino]-4-(trifluoromethoxy)phenyl}piperazin-1-yl)carbonyl]piperazine-1-carboxylate
• CAS: 1258270-43-7
• 化学式: C₃₂H₃₉F₃N₁₀O₅
• 分子量: 700.721
• InChiKey: PDIBLLHONLYXLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  50.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  164.28
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(4-{3-[(3-carbamoyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl)amino]-4-(trifluoromethoxy)phenyl}piperazin-1-yl)carbonyl]piperazine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以98%的产率得到1-methyl-8-({5-[4-(piperazin-1-ylcarbonyl)piperazin-1-yl]-2-(trifluoromethoxy)phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide hydrochloride
  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：

  tert-butyl 4-(piperazine-1-carbonyl)piperazine-1-carboxylate 、 8-{[5-bromo-2-(trifluoromethoxy)phenyl]amino}-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium hexamethyldisilazane 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以5%的产率得到tert-butyl 4-[(4-{3-[(3-carbamoyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl)amino]-4-(trifluoromethoxy)phenyl}piperazin-1-yl)carbonyl]piperazine-1-carboxylate
  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