5-(3-bromo-4-fluorophenyl)-5,11-dihydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione | 951923-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 5-(3-bromo-4-fluorophenyl)-5,11-dihydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione
• 英文别名: 2-(3-bromo-4-fluorophenyl)-5,7,9-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),3(8),11,13,15-pentaene-4,6,17-trione
• CAS: 951923-06-1
• 化学式: C₂₀H₁₁BrFN₃O₃
• 分子量: 440.228
• InChiKey: XBGBOYJIUKFYKC-UHFFFAOYSA-N

物化性质

• 密度：
  1.82±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  87.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(3-bromo-4-fluorophenyl)-5,11-dihydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione 在 四氯苯醌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.07h， 以96%的产率得到5-(3-bromo-4-fluorophenyl)-1H-indeno[2',1':5,6]pyrido[ 2,3-d]pyrimidine-2,4,6(3H)-trione
  参考文献：
  名称：

  Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 3. Fused Uracil-Containing Heterocycles as Novel Topoisomerase-Targeting Agents

  摘要：

  After the initial discovery of antiproliferative and apoptosis-inducing properties of a camptothecin-inspired pentacycle based on a 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine scaffold, a library of its analogues as well as their oxidized planar counterparts were prepared utilizing a practical multicomponent synthetic protocol. The synthesized compounds exhibited submicromolar to low micromolar antiproliferative potencies toward a panel of human cancer cell lines. Biochemical experiments are consistent with the dihydropyridine library members undergoing intracellular oxidation to the corresponding planar pyridines, which then inhibit topoisomerase II activity, leading to inhibition of proliferation and cell death. Because of facile synthetic preparation and promising antitopoisomerase activity, both the dihydropyridine and planar pyridine-based compounds represent a convenient starting point for anticancer drug discovery.

  DOI：

  10.1021/jm1009428
• 作为产物：
  描述：

  4-氨基-2,6-二羟基嘧啶 、 1,3-茚满二酮 、 3-溴-4-氟苯甲醛 在 溶剂黄146 作用下， 以 乙二醇 为溶剂， 反应 4.0h， 以68%的产率得到5-(3-bromo-4-fluorophenyl)-5,11-dihydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione
  参考文献：
  名称：

  Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 3. Fused Uracil-Containing Heterocycles as Novel Topoisomerase-Targeting Agents

  摘要：

  After the initial discovery of antiproliferative and apoptosis-inducing properties of a camptothecin-inspired pentacycle based on a 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine scaffold, a library of its analogues as well as their oxidized planar counterparts were prepared utilizing a practical multicomponent synthetic protocol. The synthesized compounds exhibited submicromolar to low micromolar antiproliferative potencies toward a panel of human cancer cell lines. Biochemical experiments are consistent with the dihydropyridine library members undergoing intracellular oxidation to the corresponding planar pyridines, which then inhibit topoisomerase II activity, leading to inhibition of proliferation and cell death. Because of facile synthetic preparation and promising antitopoisomerase activity, both the dihydropyridine and planar pyridine-based compounds represent a convenient starting point for anticancer drug discovery.

  DOI：

  10.1021/jm1009428

文献信息

• Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 3. Fused Uracil-Containing Heterocycles as Novel Topoisomerase-Targeting Agents
  作者：Nikolai M. Evdokimov、Severine Van slambrouck、Petra Heffeter、Lee Tu、Benjamin Le Calvé、Delphine Lamoral-Theys、Carla J. Hooten、Pavel Y. Uglinskii、Snezna Rogelj、Robert Kiss、Wim F. A. Steelant、Walter Berger、Jeremy J. Yang、Cristian G. Bologa、Alexander Kornienko、Igor V. Magedov

  DOI：10.1021/jm1009428

  日期：2011.4.14

  After the initial discovery of antiproliferative and apoptosis-inducing properties of a camptothecin-inspired pentacycle based on a 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine scaffold, a library of its analogues as well as their oxidized planar counterparts were prepared utilizing a practical multicomponent synthetic protocol. The synthesized compounds exhibited submicromolar to low micromolar antiproliferative potencies toward a panel of human cancer cell lines. Biochemical experiments are consistent with the dihydropyridine library members undergoing intracellular oxidation to the corresponding planar pyridines, which then inhibit topoisomerase II activity, leading to inhibition of proliferation and cell death. Because of facile synthetic preparation and promising antitopoisomerase activity, both the dihydropyridine and planar pyridine-based compounds represent a convenient starting point for anticancer drug discovery.