8-Phenyl-4,7,10-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1,6,8,11,13,15-hexaene-3,5-dione | 222636-13-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 8-Phenyl-4,7,10-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1,6,8,11,13,15-hexaene-3,5-dione
• CAS: 222636-13-7
• 化学式: C₁₉H₁₁N₃O₂
• 分子量: 313.315
• InChiKey: HWQCRZVIQIRLFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.27
• 重原子数：
  24.0
• 可旋转键数：
  1.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.85
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  8-Phenyl-4,7,10-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1,6,8,11,13,15-hexaene-3,5-dione 在 氢氧化钾 、 ammonium acetate 、 sodium hydride 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 26.0h， 生成 2,3-dihydro-6-<2-(N,N-dimethylamino)ethyl>-5-phenyl-1H,6H-pyrrolo<3',4':5,6>pyrido<3,4-b>indole-1,3-dione
  参考文献：
  名称：

  β-Carbolinedione Derivatives as Topoisomerase I Inhibitors

  摘要：

  Pyrrolo[3,4-c]-beta-carbolinedione dimers 5-14 were synthesized from furo[3,4-c]-beta-carbolinediones and diamines by solvent-free TaCl5/silica catalyzed reaction under microwave irradiation. The inhibitory property of these target compounds, the starting materials 2, 31, 32, and the N-alkylated pyrrolo[3,4-c]-beta-carbolinediones 16, 17, 20-30 was tested against the relaxation of supercoiled pRB322 DNA by calf thymus topoisomerases I and II. Some of these compounds, especially 7 and 23 proved to be selective inhibitors of topoisomerase I.

  DOI：

  10.1002/(sici)1521-4184(19997)332:7<249::aid-ardp249>3.0.co;2-f
• 作为产物：
  描述：

  3-azido-4-(3-indolyl)-pyrroline-2,5-dione 在 palladium on activated charcoal 作用下， 以 四氢呋喃 、 邻二甲苯 为溶剂， 反应 49.0h， 生成 8-Phenyl-4,7,10-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1,6,8,11,13,15-hexaene-3,5-dione
  参考文献：
  名称：

  Pyrrolo[3,4-c]-β-carboline-diones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase

  摘要：

  Members of the structurally diverse family of beta-carbolines have previously been shown to exhibit a wide range of biological activities. A novel synthetic strategy for generation of beta-carbolines was developed, allowing imido-beta-carbolines to be created in three steps from known compounds. The compounds were screened for inhibition of platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation in Swiss 3T3 fibroblasts. A number of the newly synthesized beta-carbolines with moderate to potent inhibitory activity were revealed. The most active derivative, 2,3-dihydro-8,9-dimethoxy-5-(2-methylphenyl)-1H,6H-pyrrolo[3,4-c]pyrido[3,4-b]indole-1,3-dione 2ee, inhibited purified PDGF receptor kinase and PDGF-receptor autophosphorylation in intact cells with IC50 values of 0.4 and 2.6 mu M, respectively. Dione 2ee also inhibited PDGF-stimulated DNA synthesis in Swiss 3T3 fibroblasts with an IC50 of 3.2 mu M. The compound had no effect on Src or epidermal growth factor (EGF) receptor kinase activity and a six-seven-fold higher IC50 for inhibition of basic fibroblast growth factor (bFGF)-stimulated tyrosine phosphorylation or Kit/stem cell factor (SCF) receptor autophosphorylation, indicating a reasonable extent of kinase specificity. Thus, beta-carbolines present a new lead of tyrosine kinase inhibitors with the capacity to selectively interfere with PDGF receptor signal transduction and PDGF-dependent cell growth. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00140-9