5-methoxy-6-hydroxy-7H-dibenzo[de,h]quinolin-7-one

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 异卟啉
• 英文名称: 5-methoxy-6-hydroxy-7H-dibenzo[de,h]quinolin-7-one
• 英文别名: 6-hydroxy-5-methoxy-7H-dibenzo[de,h]quinolin-7-one；5-methoxy-6-hydroxy-1-azabenzanthrone；10-hydroxy-11-methoxy-16-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2,4,6,9(17),10,12,14-octaen-8-one
• 化学式: C₁₇H₁₁NO₃
• 分子量: 277.279
• InChiKey: SAGDKDKLSFQMAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methoxy-6-hydroxy-7H-dibenzo[de,h]quinolin-7-one 在 platinum(IV) oxide 氢气 作用下， 以 溶剂黄146 为溶剂， 20.0~22.0 ℃ 、482.63 kPa 条件下， 反应 24.0h， 以32%的产率得到5-methoxy-6H-dibenzo[de,h]quinolin-6-one
  参考文献：
  名称：

  不寻常的氧代异皂啡和退火喹啉衍生物的便捷合成

  摘要：

  几种 2,3-二氢-7H-二苯并(de,h)quinolin-7-ones 和 7H-dibenzo(de,h)quinolin-7-ones 在 PtO2 上在乙酸中催化氢化得到 7-羟基喹啉和具有还原苯环的喹诺酮衍生物。有限数量的具有 7H-二苯并 (de,h) 喹啉骨架的化合物，称为 1-氮杂苯，在三十年前作为染料形成的中间体被合成，1 并且由于它们可能的光和电化学性质。2 大约在同一时间，通过 N-苯乙基邻苯二甲酰亚胺合成 7H-二苯并(de,h) 喹啉-7-one 衍生物的报道与它们可能的抗病毒活性有关，3 和一些 2,3-二氢还报道了通过环化 3-(b-二烷氧基芳基乙基氨基)邻苯二甲醚的衍生物。4 对于 5-甲氧基-2,3-二氢类似物 (2)，这种化合物的数量足够大，可以对其进行一些初步的还原研究，得到一种碱性甲醇，但其结构尚未得到充分证实。自 1980 年代以来，已从 Menispermum

  DOI：

  10.1055/s-2003-41422
• 作为产物：
  描述：

  6,7-dimethoxy-1-<(ortho-bromo)phenyl>-3,4-dihydroisoquinoline 在 氨 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.0h， 生成 5-methoxy-6-hydroxy-7H-dibenzo[de,h]quinolin-7-one
  参考文献：
  名称：

  Synthesis and antiplasmodial activity of some 1-azabenzanthrone derivatives

  摘要：

  Some synthetic 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones) are weakly to moderately cytotoxic, suggesting that they might also show antiparasitic activity. We have now tested a small collection of these compounds in vitro against a chloroquine-resistant Plasmodium falciparum strain, comparing their cytotoxicity against normal human fibroblasts. Our results indicate that 5-methoxy-1-azabenzanthrone and its 2,3-dihydro analogue have low micromolar antiplasmodial activities and showed more than 10-fold selectivity against the parasite, indicating that the dihydro compound, in particular, might serve as a lead compound for further development. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.092

文献信息

• Annulation of substituted anthracene-9,10-diones yields promising selectively antiproliferative compounds
  作者：Vicente Castro-Castillo、Cristian Suárez-Rozas、Natalia Castro-Loiza、Cristina Theoduloz、Bruce K. Cassels

  DOI：10.1016/j.ejmech.2013.01.049

  日期：2013.4

  Anthraquinone derivatives are well-known antiproliferative compounds, and some are currently used in cancer chemotherapy. Some families of annulated anthraquinone analogs have also been examined for antiproliferative activity, but in this regard almost nothing is known of 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones). A series of 1-azabenzanthrone derivatives, their 2,3-dihydro analogs, and

  蒽醌衍生物是众所周知的抗增殖化合物，目前一些被用于癌症化学疗法中。还已经研究了一些环状的蒽醌​​类似物的抗增殖活性，但是在这方面，几乎没人知道1-氮杂苯并蒽酮（7 H-二苯并[ de，h ]喹啉-7-酮）。测试了一系列的1-氮杂苯并蒽醌衍生物，它们的2,3-二氢类似物和同等取代的9,10-蒽二酮对正常的人类成纤维细胞和四种人类癌细胞系。多数杂环化合物被证明对IC 50具有弱至中度的抗增殖作用该值向下延伸至0.86μM，并且在癌症和正常细胞之间表现出高达30倍的选择性。1-氮杂苯并蒽酮和1-氮杂-2,3-二氢苯并蒽酮均比蒽醌类更有效，几乎毫无例外，2,3-二氢化合物比完全芳族的1-氮杂苯并蒽酮更有效。
• Synthesis and total assignment of1H and13C NMR spectra of new oxoisoaporphines by long-range heteronuclear correlations
  作者：Eduardo Sobarzo-Sánchez、Julio De la Fuente、Luis Castedo

  DOI：10.1002/mrc.1703

  日期：2005.12

  new oxoisoaporphines 7H‐dibenzo[de,h]quinolin‐7‐one, 5‐methoxy‐7H‐dibenzo[de,h]quinolin‐7‐one, 5‐methoxy‐6‐hydroxy‐7H‐dibenzo[de,h]quinolin‐7‐one, 5‐hydroxy‐7H‐dibenzo[de,h]quinolin‐7‐one and 5‐methoxy‐6H‐dibenzo[de,h]quinolin‐6‐one were prepared either by oxidation of their 2,3‐dihydro derivatives or by heating (2′‐(3,4‐dihydro‐6,7‐dimethoxyisoquinolin‐1′‐yl)phenyl)methylbenzoate with an acetic acid/sulfuric

  新型氧代异皂啡类 7H-二苯并[de,h]quinolin-7-one, 5-甲氧基-7H-二苯并[de,h]quinolin-7-one, 5-甲氧基-6-羟基-7H-二苯并[de,h] ]喹啉-7-酮、5-羟基-7H-二苯并[de,h]喹啉-7-one和5-甲氧基-6H-二苯并[de,h]喹啉-6-酮是通过将它们的 2 ,3-二氢衍生物或通过在 100 °C 下加热（2'-（3,4-二氢-6,7-二甲氧基异喹啉-1'-基）苯基）甲基苯甲酸酯与乙酸/硫酸混合物。结构得到确认，1H 和 13C NMR 光谱使用二维 NMR 技术完全确定。版权所有 © 2005 John Wiley & Sons, Ltd.
• Metal free synthesis of functionalized 1-aryl isoquinolines via iodine mediated oxidative dehydrogenation and ring opening of lactam in isoindoloisoquinolinones
  作者：Kamsali Murali Mohan Achari、Muthupandi Karthick、Chinnasamy Ramaraj Ramanathan

  DOI：10.1007/s12039-017-1301-7

  日期：2017.6

  facile and convenient method for the synthesis of substituted 2-(isoquinolin-1-yl)benzoic acids from isoindoloisoquinolinones in the presence of molecular iodine under sealed tube condition at 100\(^\circ }\hbox C}\) has been developed. This methodology involves the oxidative dehydrogenation and ring opening of hydroxy lactam/methoxy lactam to furnish the 2-(isoquinolin-1-yl)benzoic acids. Some of

  摘要一种用于合成容易且方便的方法，取代的2-（异喹啉-1-基）从在100中密封管条件下，分子碘的存在isoindoloisoquinolinones苯甲酸\（^ \ CIRC} \ hbox中C} \）具有已开发。该方法涉及羟基内酰胺/甲氧基内酰胺的氧化脱氢和开环以提供2-（异喹啉-1-基）苯甲酸。这些酸中的一些已成功环化，以提供氮杂苯并蒽醌衍生物，这是合成半月板碱生物碱和柔红霉素异四氢萘的潜在前体。 图形概要 提要报道了在密封管条件下，使用碘从异吲哚异喹啉酮类化合物无金属合成1-芳基异喹啉或氮杂苯甲酮类化合物的合成前体。该方法被成功地用于合成1-氮杂苯并蒽醌和半月板碱的类似物，即5-甲氧基-6-羟基-1-氮杂苯并蒽醌。
• New Approaches to 6-Oxoisoaporphine and Tetrahydroisoquinoline Derivatives
  作者：Eduardo Sobarzo-Sánchez、Eugenio Uriarte、Lourdes Santana、Ricardo A. Tapia、Paulo Pérez Lourido

  DOI：10.1002/hlca.200900394

  日期：——

  starting materials to afford 6‐oxoisoaporphine and 2,3‐dimethoxy‐5,6,8,12b‐tetrahydroisoindolo[1,2‐a]isoquinoline as the main products. However, the catalytic hydrogenation of the benzyl benzoate derivative afforded, under mild conditions, 1,2,3,4‐tetrahydro‐6,7‐dimethoxy‐1‐(2‐methylphenyl)isoquinoline.

  2,3-二氢-6-羟基-5-甲氧基-7- ħ -二苯并[德，ħ ]喹啉-7-酮，6-羟基-5-甲氧基-7- ħ -二苯并[德，ħ ]喹啉-7-一和2-（6,7-二甲氧基-3,4-二氢异喹啉-1-基）苯甲酸苄酯（可通过Bischler-Napieralski环化轻松获得）用作起始原料，可制得6-氧代异吗啡和2,3-二甲氧基‐5,6,8,12b-四氢异吲哚并[1,2- a ]异喹啉为主要产品。但是，在温和条件下苯甲酸苄酯衍生物的催化加氢提供了1,2,3,4-四氢-6,7-二甲氧基-1-（2-甲基苯基）异喹啉。
• 2D MI-DRAGON: A new predictor for protein–ligands interactions and theoretic-experimental studies of US FDA drug-target network, oxoisoaporphine inhibitors for MAO-A and human parasite proteins
  作者：Francisco Prado-Prado、Xerardo García-Mera、Manuel Escobar、Eduardo Sobarzo-Sánchez、Matilde Yañez、Pablo Riera-Fernandez、Humberto González-Díaz

  DOI：10.1016/j.ejmech.2011.09.045

  日期：2011.12

  There are many pairs of possible Drug-Proteins Interactions that may take place or not (DPIs/nDPIs) between drugs with high affinity/non-affinity for different proteins. This fact makes expensive in terms of time and resources, for instance, the determination of all possible ligands-protein interactions for a single drug. In this sense, we can use Quantitative Structure-Activity Relationships (QSAR) models to carry out rational DPIs prediction. Unfortunately, almost all QSAR models predict activity against only one target. To solve this problem we can develop multi-target QSAR (mt-QSAR) models. In this work, we introduce the technique 2D MI-DRAGON a new predictor for DPIs based on two different well-known software. We use the software MARCH-INSIDE (MI) to calculate 3D structural parameters for targets and the software DRAGON was used to calculated 2D molecular descriptors all drugs showing known DPIs present in the Drug Bank (US FDA benchmark dataset). Both classes of parameters were used as input of different Artificial Neural Network (ANN) algorithms to seek an accurate non-linear mt-QSAR predictor. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 21:21-31-1:1. This MLP classifies correctly 303 out of 339 DPIs (Sensitivity = 89.38%) and 480 out of 510 nDPIs (Specificity = 94.12%), corresponding to training Accuracy = 92.23%. The validation of the model was carried out by means of external predicting series with Sensitivity = 92.18% (625/678 DPIs: Specificity = 90.12% (730/780 nDPIs) and Accuracy = 91.06%. 2D MI-DRAGON offers a good opportunity for fast-track calculation of all possible DPIs of one drug enabling us to re-construct large drug-target or DPIs Complex Networks (CNs). For instance, we reconstructed the CN of the US FDA benchmark dataset with 855 nodes 519 drugs + 336 targets). We predicted CN with similar topology (observed and predicted values of average distance are equal to 6.7 vs. 6.6). These CNs can be used to explore large DPIs databases in order to discover both new drugs and/or targets. Finally, we illustrated in one theoretic-experimental study the practical use of 2D MI-DRAGON. We reported the prediction, synthesis, and pharmacological assay of 10 different oxoisoaporphines with MAO-A inhibitory activity. The more active compound OXO5 presented IC50 = 0.00083 mu M, notably better than the control drug Clorgyline. (C) 2011 Elsevier Masson SAS. All rights reserved.