5,6-dihydro-6-[3-(2-hydroxyethyl)amino-1-propyl]-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-(2-hydroxyethyl)amino-1-propyl]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
• 英文别名: 6-[3-(2-hydroxyethyl)aminopropyl]-5,11-dioxo-5,6-dihydro-11H-indeno[1,2-c]isoquinoline；6-[3-(2-Hydroxyethylamino)propyl]indeno[1,2-c]isoquinoline-5,11-dione
• 化学式: C₂₁H₂₀N₂O₃
• 分子量: 348.401
• InChiKey: BYCJOFWNTUNYGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  C.I.酸性橙108 、 6-(3-bromo-1-propyl)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 以 二甲基亚砜 为溶剂， 反应 35.0h， 生成 5,6-dihydro-6-[3-(2-hydroxyethyl)amino-1-propyl]-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Nitrated Indenoisoquinolines as Topoisomerase I Inhibitors:  A Systematic Study and Optimization

  摘要：

  The biological activity of indenoisoquinoline topoisomerase I (Topl) inhibitors can be greatly enhanced depending on the choice of substituents on the aromatic rings and lactam side chain. Previously, it was discovered that a 3-nitro group and a 9-methoxy group afforded enhanced biological activity. In the present investigation, indenoisoquinoline analogues were systematically prepared using combinations of nitro groups, methoxy groups, and hydrogen atoms in an effort to understand the contribution of each group toward cytotoxicity and Top I inhibition. Analysis of the biological results suggests that the nitro group is important for Top I inhibition and the methoxy group improves cytotoxicity. In addition, previously identified structure-activity relationships were utilized to select favorable lactam side chain functionalities for incorporation on the aromatic skeleton of analogues in this study. As a result, this investigation has provided optimal Topl inhibitors equipotent to camptothecin that demonstrate low nanomolar cytotoxicities toward cancer cells.

  DOI：

  10.1021/jm070361q

文献信息

• 6-(2-HYDROXYETHYLAMINOALKYL)-5,11-DIOXO-5,6-DIHYDRO-11H- INDENO[1,2-C]ISOQUINOLINES AND THEIR USE AS ANTINEOPLASTIC AGENTS
  申请人：VUFB, a.s.

  公开号：EP0643699B1

  公开（公告）日：1996-10-23
• PATIENT SELECTION FOR TREATMENT OF MYC POSITIVE CANCERS WITH INDENOISOQUINOLINES
  申请人：Purdue Research Foundation

  公开号：US20210382058A1

  公开（公告）日：2021-12-09

  The present disclosure is directed to a method for selecting a patient with cancer for treatment with a compound of formula (I) by determining if the patient's cancer cells are MYC-positive and when the MYC promoter sequence in those cancer cells contains a nucleic acid sequence capable of forming a MYC G-quadruplex (MYC G4) (i.e. are MYC G4-positive) and treating the patient with a compound of formula (I).
• US5597831A
  申请人：——

  公开号：US5597831A

  公开（公告）日：1997-01-28