2,4-di-n-hexyl-8,9,10,11-tetrahydro-8,11-methanobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraone | 1600523-60-1

• 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: 2,4-di-n-hexyl-8,9,10,11-tetrahydro-8,11-methanobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraone
• 英文别名: 7,9-Dihexyl-7,9,11-triazapentacyclo[14.2.1.02,15.04,13.05,10]nonadeca-2(15),4,10,12-tetraene-3,6,8,14-tetrone；7,9-dihexyl-7,9,11-triazapentacyclo[14.2.1.02,15.04,13.05,10]nonadeca-2(15),4,10,12-tetraene-3,6,8,14-tetrone
• CAS: 1600523-60-1
• 化学式: C₂₈H₃₅N₃O₄
• 分子量: 477.604
• InChiKey: JLNUJOOIKFHBKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  87.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5,8-dihydroxy-1,2,3,4-tetrahydro-1,4-methanonaphthalene-6-carboxaldehyde 、 6-Amino-1,3-dihexylpyrimidine-2,4(1H,3H)-dione 在 magnesium sulfate 、 silver(l) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以93%的产率得到2,4-di-n-hexyl-8,9,10,11-tetrahydro-8,11-methanobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraone
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2014.03.024

文献信息

• 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.