4,6-二氯-5-甲氧基-1,3-苯硼酸频哪醇酯 | 1221589-79-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4,6-二氯-5-甲氧基-1,3-苯硼酸频哪醇酯
• 英文名称: 2,2'-(4,6-dichloro-5-methoxy-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)
• 英文别名: 2-[2,4-dichloro-3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• CAS: 1221589-79-2
• 化学式: C₁₉H₂₈B₂Cl₂O₅
• 分子量: 428.956
• InChiKey: TYZSIKCUEYRUDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  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 、 salcomine 、 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 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 20.33h， 生成 deoxynyboquinone
  参考文献：
  名称：

  [EN] COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES
  [FR] COMPOSÉS ET SUBSTRATS ANTITUMORAUX NQO1

  摘要：

  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。

  公开号：

  WO2013056073A1
• 作为产物：
  描述：

  (4,6-dichloro-5-methoxy-1,3-phenylene)bis(trimethylsilane) 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 一氯化碘 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 24.08h， 生成 4,6-二氯-5-甲氧基-1,3-苯硼酸频哪醇酯
  参考文献：
  名称：

  [EN] COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES
  [FR] COMPOSÉS ET SUBSTRATS ANTITUMORAUX NQO1

  摘要：

  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。

  公开号：

  WO2013056073A1

文献信息

• [EN] TOPOISOMERASE INHIBITORS WITH ANTIBACTERIAL AND ANTCANCER ACTIVITY<br/>[FR] INHIBITEURS DE LA TOPOISOMÉRASE AYANT UNE ACTIVITÉ ANTIBACTÉRIENNE ET UNE ACTIVITÉ ANTI-CANCÉREUSE
  申请人：UNIV ILLINOIS

  公开号：WO2018237140A1

  公开（公告）日：2018-12-27

  Inhibitors of human topoisomerase II (Top2) are the backbone of numerous cancer chemotherapy regimens. Unfortunately, the onset of toxicity severely limits the utility of these powerful drugs. There is some conservation between human Top2 and bacterial homologues (DNA gyrase and TopoIV). Thus, the conversion of antibacterial topoisomerase inhibitors into antineoplastic agents is an intriguing strategy for anticancer compounds. Herein is described the conversion of deoxynybomycin (DNM), a natural product and DNA gyrase inhibitor with minimal cytotoxicity, into a compound that has anticancer activity. Detailed in vitro and cell culture experiments demonstrate that these compounds inhibit Top2 and also act upon topoisomerase I. Similar approaches are applicable to other classes of gyrase inhibitors and other antibacterial targets for discovery of new anticancer drugs.

  人类拓扑异构酶II（Top2）的抑制剂是许多癌症化疗方案的基础。不幸的是，毒性的发生严重限制了这些强效药物的实用性。人类Top2和细菌同源物（DNA旋转酶和TopoIV）之间存在一定的保守性。因此，将抗菌拓扑异构酶抑制剂转化为抗肿瘤药物是一种有趣的抗癌化合物策略。本文描述了将脱氧尼伯霉素（DNM），一种天然产物和DNA旋转酶抑制剂，转化为具有抗癌活性的化合物。详细的体外和细胞培养实验证明这些化合物抑制Top2，同时也对拓扑异构酶I起作用。类似的方法适用于其他类别的旋转酶抑制剂和其他抗菌靶标，用于发现新的抗癌药物。
• Chemistry and Biology of Deoxynyboquinone, a Potent Inducer of Cancer Cell Death
  作者：Joseph S. Bair、Rahul Palchaudhuri、Paul J. Hergenrother

  DOI：10.1021/ja100610m

  日期：2010.4.21

  Deoxynyboquinone (DNQ) is a potent antineoplastic agent with an unknown mechanism of action. Here we describe a facile synthetic route to this anthraquinone, and we use this material to determine the mechanism by which DNQ induces death in cancer cells. DNQ was synthesized in seven linear steps through a route employing three palladium-mediated coupling reactions. Experiments performed on cancer cells grown in hypoxia and normoxia strongly suggest that DNQ undergoes bioreduction to its semiquinone, which then is re-oxidized by molecular oxygen, forming superoxide that induces cell death. Furthermore, global transcript profiling of cells treated with DNQ shows elevation of transcripts related to oxidative stress, a result confirmed at the protein level by Western blotting. In contrast to most other antineoplastic agents that generate reactive oxygen species (ROS), DNQ potently induces death of cancer cells in culture, with IC50 values between 16 and 210 nM. In addition, unlike the experimental therapeutic elesclomol, DNQ is still able to induce cancer cell death under hypoxic conditions. This mechanistic understanding of DNQ will allow for a more comprehensive evaluation of the potential of direct ROS generation as an anticancer strategy, and DNQ itself has potential as a novel anticancer agent.
• Efficient NQO1 Substrates are Potent and Selective Anticancer Agents
  作者：Elizabeth I. Parkinson、Joseph S. Bair、Megan Cismesia、Paul J. Hergenrother

  DOI：10.1021/cb4005832

  日期：2013.10.18

  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.
• [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。