5,6-dihydro-6-(3-(1H-imidazol-1-yl)propyl)-3-iodo-5,11-dioxo-11H-indeno[1,2-c]isoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 5,6-dihydro-6-(3-(1H-imidazol-1-yl)propyl)-3-iodo-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
• 英文别名: 6-(3-Imidazol-1-ylpropyl)-3-iodoindeno[1,2-c]isoquinoline-5,11-dione；6-(3-imidazol-1-ylpropyl)-3-iodoindeno[1,2-c]isoquinoline-5,11-dione
• 化学式: C₂₂H₁₆IN₃O₂
• 分子量: 481.292
• InChiKey: BEKNICLTBJPRSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-氨基四氯苯酞 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 sodium methylate 、 potassium hydroxide 、 sodium nitrite 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 、 氯仿 、 水 、 乙酸乙酯 为溶剂， 反应 72.42h， 生成 5,6-dihydro-6-(3-(1H-imidazol-1-yl)propyl)-3-iodo-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Discovery of Potent Indenoisoquinoline Topoisomerase I Poisons Lacking the 3-Nitro Toxicophore

  摘要：

  3-Nitroindenoisoquinoline human topoisomerase IB (Top1) poisons have potent antiproliferative effects on cancer cells. The undesirable nitro toxicophore could hypothetically be replaced by other functional groups that would retain the desired biological activities and minimize potential safety risks. Eleven series of indenoisoquinolines bearing 3-nitro bioisosteres were synthesized. The molecules were evaluated in the Top1-mediated DNA cleavage assay and in the National Cancer Institute's 60 cell line cytotoxicity assay. The data reveal that fluorine and chlorine may substitute for the 3-nitro group with minimal loss of Top1 poisoning activity. The new information gained from these efforts can be used to design novel indenoisoquinolines with improved safety.

  DOI：

  10.1021/acs.jmedchem.5b00303

文献信息

• Discovery of Potent Indenoisoquinoline Topoisomerase I Poisons Lacking the 3-Nitro Toxicophore
  作者：Daniel E. Beck、Monica Abdelmalak、Wei Lv、P. V. Narasimha Reddy、Gabrielle S. Tender、Elizaveta O’Neill、Keli Agama、Christophe Marchand、Yves Pommier、Mark Cushman

  DOI：10.1021/acs.jmedchem.5b00303

  日期：2015.5.14

  3-Nitroindenoisoquinoline human topoisomerase IB (Top1) poisons have potent antiproliferative effects on cancer cells. The undesirable nitro toxicophore could hypothetically be replaced by other functional groups that would retain the desired biological activities and minimize potential safety risks. Eleven series of indenoisoquinolines bearing 3-nitro bioisosteres were synthesized. The molecules were evaluated in the Top1-mediated DNA cleavage assay and in the National Cancer Institute's 60 cell line cytotoxicity assay. The data reveal that fluorine and chlorine may substitute for the 3-nitro group with minimal loss of Top1 poisoning activity. The new information gained from these efforts can be used to design novel indenoisoquinolines with improved safety.