1-hexyl-4,6-dimethyl-9H-pyrido[3,2-g]quinoline-2,5,8,10-tetrone | 1430798-15-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-hexyl-4,6-dimethyl-9H-pyrido[3,2-g]quinoline-2,5,8,10-tetrone
• CAS: 1430798-15-4
• 化学式: C₂₀H₂₂N₂O₄
• 分子量: 354.406
• InChiKey: SIWOBPMWEBFAPX-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：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,6-二氯-5-甲氧基-1,3-苯硼酸频哪醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 [N,N'-bis(salicylidene)ethane-1,2-diaminato]cobalt(II) 、 氢溴酸 、 氧气 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 1-hexyl-4,6-dimethyl-9H-pyrido[3,2-g]quinoline-2,5,8,10-tetrone
  参考文献：
  名称：

  Efficient NQO1 Substrates are Potent and Selective Anticancer Agents

  摘要：

  A major goal of personalized medicine in oncology is the identification of drugs with predictable efficacy based on a specific trait of the cancer cell, as has been demonstrated with gleevec (presence of Bcr-Abl protein), herceptin (Her2 overexpression), and iressa (presence of a specific EGFR mutation). This is a challenging task, as it requires identifying a cellular component that is altered in cancer, but not normal cells, and discovering a compound that specifically interacts with it. The enzyme NQO1 is a potential target for personalized medicine, as it is overexpressed in many solid tumors. In normal cells NQO1 is inducibly expressed, and its major role is to detoxify quinones via bioreduction; however, certain quinones become more toxic after reduction by NQO1, and these compounds have potential as selective anticancer agents. Several quinones of this type have been reported, including mitomycin C, RH1, EO9, streptonigrin, beta-lapachone, and deoxynyboquinone (DNQ). However, no unified picture has emerged from these studies, and the key question regarding the relationship between NQO1 processing and anticancer activity remains unanswered. Here, we directly compare these quinones as substrates for NQO1 in vitro, and for their ability to kill cancer cells in culture in an NQO1-dependent manner. We show that DNQ is a superior NQO1 substrate, and we use computationally guided design to create DNQ analogues that have a spectrum of activities with NQO1. Assessment of these compounds definitively establishes a strong relationship between in vitro NQO1 processing and induction of cancer cell death and suggests these compounds are outstanding candidates for selective anticancer therapy.

  DOI：

  10.1021/cb4005832

文献信息

• [EN] COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES<br/>[FR] COMPOSÉS ET SUBSTRATS ANTITUMORAUX NQO1
  申请人：UNIV ILLINOIS

  公开号：WO2013056073A1

  公开（公告）日：2013-04-18

  Compounds of Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compounds are useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.

  化合物的化学式（I）可以选择性地对多种不同类型的癌细胞具有致命作用。这些化合物对于管理、治疗、控制或辅助治疗疾病非常有用，其中选择性的致命作用在化疗疗法中具有益处。
• Tumor-selective combination therapy
  申请人：The Board of Regents of the University of Texas System

  公开号：US10272099B2

  公开（公告）日：2019-04-30

  The therapies described herein can be selectively lethal toward a variety of different cancer cell types and cancer conditions in a subject. The combination therapies described herein can be useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy, particularly where the disease is accompanied by elevated levels of NQO1.

  本文所述的疗法可以选择性地杀死受试者体内各种不同的癌细胞类型和癌症病症。本文所述的组合疗法可用于疾病的管理、治疗、控制或辅助治疗，其中选择性致死在化疗中是有益的，特别是在疾病伴有 NQO1 水平升高的情况下。
• Compounds and anti-tumor NQO1 substrates
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10285986B2

  公开（公告）日：2019-05-14

  Compositions comprising Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compositions are useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.

  由式（I）组成的组合物可对多种不同类型的癌细胞产生选择性杀伤作用。这些组合物可用于疾病的管理、治疗、控制或辅助治疗，其中选择性致死在化疗中是有益的。
• COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2768308B1

  公开（公告）日：2018-04-18
• USE OF DNQ OR DNQ-87 IN COMBINATION WITH A PARP1 INHIBITOR FOR THE TREATMENT OF CANCER
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2984184B1

  公开（公告）日：2020-11-25