5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-methanonaphthalene-6-carboxaldehyde | 952006-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-methanonaphthalene-6-carboxaldehyde
• 英文别名: 3,6-Dimethoxytricyclo[6.2.1.02,7]undeca-2,4,6-triene-4-carbaldehyde
• CAS: 952006-62-1
• 化学式: C₁₄H₁₆O₃
• 分子量: 232.279
• InChiKey: YRFFFCLPSKRRBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-methanonaphthalene-6-carboxaldehyde 在 ammonium cerium (IV) nitrate 、 对甲苯磺酸 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 4.05h， 生成 6-(1,3-dioxolan-2-yl)-1,2,3,4-tetrahydro-1,4-methanonaphthalene-5,8-dione
  参考文献：
  名称：

  1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as New Leads against Mycobacterium tuberculosis

  摘要：

  Tuberculosis (TB) continues to be a worldwide health problem with over 1.4 million deaths each year. Despite efforts to develop more effective vaccines, more reliable diagnostics, and chemotherapeutics, tuberculosis remains a threat to global health, fueled by the HIV pandemic and the rapid generation of drug resistance. The exploration of novel drugs to serve as a companion drug for existing drugs is of paramount importance. As part of our program to design new 2-aza-anthraquinones with antimycobacterial activity, various tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. These compounds showed high in vitro potency against Mycobacterium tuberculosis, the etiological agent of TB and against other clinically relevant mycobacterial species at submicromolar concentrations. The susceptibility of a multidrug resistant strain toward these compounds and their ability to target intracellular replicating Mycobacterium tuberculosis was demonstrated. Next to the acute toxicity, the genotoxicity of these compounds was investigated. Often overlooked in studies, genotoxicity could be dismissed for the investigated compounds, making them a promising scaffold in TB drug research.

  DOI：

  10.1021/jm401735w
• 作为产物：
  描述：

  在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 3.0h， 以96%的产率得到5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-methanonaphthalene-6-carboxaldehyde
  参考文献：
  名称：

  1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as New Leads against Mycobacterium tuberculosis

  摘要：

  Tuberculosis (TB) continues to be a worldwide health problem with over 1.4 million deaths each year. Despite efforts to develop more effective vaccines, more reliable diagnostics, and chemotherapeutics, tuberculosis remains a threat to global health, fueled by the HIV pandemic and the rapid generation of drug resistance. The exploration of novel drugs to serve as a companion drug for existing drugs is of paramount importance. As part of our program to design new 2-aza-anthraquinones with antimycobacterial activity, various tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. These compounds showed high in vitro potency against Mycobacterium tuberculosis, the etiological agent of TB and against other clinically relevant mycobacterial species at submicromolar concentrations. The susceptibility of a multidrug resistant strain toward these compounds and their ability to target intracellular replicating Mycobacterium tuberculosis was demonstrated. Next to the acute toxicity, the genotoxicity of these compounds was investigated. Often overlooked in studies, genotoxicity could be dismissed for the investigated compounds, making them a promising scaffold in TB drug research.

  DOI：

  10.1021/jm401735w

文献信息

• The synthesis and in vitro biological evaluation of novel fluorinated tetrahydrobenzo[j]phenanthridine-7,12-diones against Mycobacterium tuberculosis
  作者：Davie Cappoen、Eveline Torfs、Tamara Meiresonne、Pieter Claes、Elena Semina、Francis Holvoet、Maíra Bidart de Macedo、Freya Cools、Tatiana Piller、An Matheeussen、Kevin Van Calster、Guy Caljon、Peter Delputte、Louis Maes、Olivier Neyrolles、Norbert De Kimpe、Sven Mangelinckx、Paul Cos

  DOI：10.1016/j.ejmech.2019.07.052

  日期：2019.11

  Tuberculosis (TB) still has a major impact on public health. In order to efficiently eradicate this life-threatening disease, the exploration of novel anti TB drugs is of paramount importance. As part of our program to design new 2-azaanthraquinones with anti-mycobacterial activity, various "out-of-plane" tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. In this study, the scaffold of the most promising hits was further optimized in an attempt to improve the bioactivity and to decrease enzymatic degradation. The rudiment bio-evaluation of a small library of fluorinated tetrahydrobenzo[j] phenanthridine-7,12-dione derivatives indicated no significant improvement of the bio-activity against intracellular and extracellular Mycobacterium tuberculosis (Mtb). Though, the derivatives showed an acceptable toxicity against J774A.1 macrophages and early signs of genotoxicity were absent. All derivatives showed to be metabolic stabile in the presence of both phase I and phase II murine or human microsomes. Finally, the onset of reactive oxygen species within Mtb after exposure to the derivatives was measured by electron paramagnetic resonance (EPR). Results showed that the most promising fluorinated derivative is still a possible candidate for the subversive inhibition of mycothione reductase. (C) 2019 Elsevier Masson SAS. All rights reserved.
• 2,4-Dialkyl-8,9,10,11-tetrahydrobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraones as new leads against Mycobacterium tuberculosis
  作者：Pieter Claes、Davie Cappoen、Cynthia Uythethofken、Jan Jacobs、Birgit Mertens、Vanessa Mathys、Luc Verschaeve、Kris Huygen、Norbert De Kimpe

  DOI：10.1016/j.ejmech.2014.03.024

  日期：2014.4

  Given the re-emergence of tuberculosis in Europe and beyond, the search for novel bio-active compound classes against this disease is of utmost importance. As a result of a high intrinsic tolerance of the etiological agent, Mycobacterium tuberculosis, towards most antibiotics and xenobiotics, the search for such new compounds is far from trivial. Further exacerbated by the rapid generation and spread of drug resistant M. tuberculosis and fuelled by the HIV/AIDS pandemic, halting the tuberculosis epidemic is of paramount importance. As part of our program to design new 2-aza-anthraquinones with anti-mycobacterial activity, various dialkyltetrahydrobenzo[g]pyrimido[4,5-c]lisoquinolinetetraones were designed and synthesised. The compounds were submitted to a biological evaluation in which the activity against M.tb H37Rv(lux) was observed, as well as the acute toxicity towards J774 A.1 macrophages. From these results, the selectivity index was calculated. Furthermore, the activity of the most promising compounds was further studied against a multi-drug resistant LAM-1 strain and against intracellular replicating M.tb. The study was further extended with a comet assay and a VITOTOX (TM) assay to investigate the possibility of observable genotoxic effects caused by these compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 1,2,3,4,8,9,10,11-Octahydrobenzo[<i>j</i>]phenanthridine-7,12-diones as New Leads against <i>Mycobacterium tuberculosis</i>
  作者：Davie Cappoen、Pieter Claes、Jan Jacobs、Roel Anthonissen、Vanessa Mathys、Luc Verschaeve、Kris Huygen、Norbert De Kimpe

  DOI：10.1021/jm401735w

  日期：2014.4.10

  Tuberculosis (TB) continues to be a worldwide health problem with over 1.4 million deaths each year. Despite efforts to develop more effective vaccines, more reliable diagnostics, and chemotherapeutics, tuberculosis remains a threat to global health, fueled by the HIV pandemic and the rapid generation of drug resistance. The exploration of novel drugs to serve as a companion drug for existing drugs is of paramount importance. As part of our program to design new 2-aza-anthraquinones with antimycobacterial activity, various tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. These compounds showed high in vitro potency against Mycobacterium tuberculosis, the etiological agent of TB and against other clinically relevant mycobacterial species at submicromolar concentrations. The susceptibility of a multidrug resistant strain toward these compounds and their ability to target intracellular replicating Mycobacterium tuberculosis was demonstrated. Next to the acute toxicity, the genotoxicity of these compounds was investigated. Often overlooked in studies, genotoxicity could be dismissed for the investigated compounds, making them a promising scaffold in TB drug research.