7-硝基-4-氧代-1H-喹啉-3-羧酸 | 40107-11-7

• 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
• 中文名称: 7-硝基-4-氧代-1H-喹啉-3-羧酸
• 英文名称: 3-carboxy-4-hydroxy-7-nitroquinoline
• 英文别名: 4-hydroxy-7-nitroquinoline-3-carboxylic acid；4-Hydroxy-7-nitrochinolin-3-carboxylsaeure；4-hydroxy-7-nitro-3-quinolinecarboxylic acid；7-nitro-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 40107-11-7
• 化学式: C₁₀H₆N₂O₅
• mdl: MFCD11042700
• 分子量: 234.168
• InChiKey: HGHKRTOZDXYURD-UHFFFAOYSA-N

物化性质

• 熔点：
  274-275 °C (decomp)
• 沸点：
  478.2±45.0 °C(Predicted)
• 密度：
  1.677±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-硝基-4-氧代-1H-喹啉-3-羧酸 在 三氯氧磷 作用下， 以 二苯醚 为溶剂， 反应 1.8h， 生成 4-氯-7-硝基喹啉
  参考文献：
  名称：

  4-[(Quinolin-4-yl)amino]苯甲酰胺衍生物作为新型抗流感病毒药物的设计、合成、分子对接分析和生物学评价

  摘要：

  本研究设计合成了一系列4-[(quinolin-4-yl)amino]苯甲酰胺衍生物作为新型抗流感药物。进行细胞毒性试验、细胞病变效应试验和噬斑抑制试验以评估目标化合物的抗流感病毒 A/WSN/33 (H1N1) 活性。目标化合物G07在细胞病变效应试验 (EC 50 = 11.38 ± 1.89 µM) 和噬菌斑抑制试验 (IC 50 = 0.23 ± 0.15 µM)中均表现出显着的抗流感病毒 A/WSN/33 (H1N1) 活性。G07对其他三种不同的流感病毒株 A/PR/8 (H1N1)、A/HK/68 (H3N2) 和乙型流感病毒也表现出显着的抗流感病毒活性。根据核糖核蛋白重组试验结果，G07与核糖核蛋白相互作用良好，在100 µM时抑制率为80.65%。此外，根据最佳药效团 Hypo1 预测的 PA-PB1 抑制活性， G07表现出显着的活性靶标 RNA 聚合酶 PA-PB1

  DOI：

  10.3390/ijms23116307
• 作为产物：
  描述：

  二乙基(3-硝基苯胺亚甲基)丙二酸 在 水 、 sodium hydroxide 作用下， 以 二苯醚 为溶剂， 反应 6.8h， 生成 7-硝基-4-氧代-1H-喹啉-3-羧酸
  参考文献：
  名称：

  4-[(Quinolin-4-yl)amino]苯甲酰胺衍生物作为新型抗流感病毒药物的设计、合成、分子对接分析和生物学评价

  摘要：

  本研究设计合成了一系列4-[(quinolin-4-yl)amino]苯甲酰胺衍生物作为新型抗流感药物。进行细胞毒性试验、细胞病变效应试验和噬斑抑制试验以评估目标化合物的抗流感病毒 A/WSN/33 (H1N1) 活性。目标化合物G07在细胞病变效应试验 (EC 50 = 11.38 ± 1.89 µM) 和噬菌斑抑制试验 (IC 50 = 0.23 ± 0.15 µM)中均表现出显着的抗流感病毒 A/WSN/33 (H1N1) 活性。G07对其他三种不同的流感病毒株 A/PR/8 (H1N1)、A/HK/68 (H3N2) 和乙型流感病毒也表现出显着的抗流感病毒活性。根据核糖核蛋白重组试验结果，G07与核糖核蛋白相互作用良好，在100 µM时抑制率为80.65%。此外，根据最佳药效团 Hypo1 预测的 PA-PB1 抑制活性， G07表现出显着的活性靶标 RNA 聚合酶 PA-PB1

  DOI：

  10.3390/ijms23116307

文献信息

• Synthesis of 1,4-Dihydro-4-oxo-quinoline-3-carboxylic Acid Derivatives as Inhibitors of Rat Lens Aldose Reductase
  作者：Erdem Büyükbingöl、Net Daş、Gilles Klopman

  DOI：10.1002/ardp.19943270302

  日期：——

  The title compounds were prepared according to Scheme 2 and tested as inhibitors of the aldose reductase of rat lens.

  根据方案2制备标题化合物并作为大鼠晶状体醛糖还原酶的抑制剂进行测试。
• 4-HYDROXYQUINOLINE-3-CARBOXAMIDES AND HYDRAZIDES AS ANTIVIRAL AGENTS
  申请人：Pharmacia & Upjohn Company LLC

  公开号：EP1042295B1

  公开（公告）日：2005-09-07
• Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods
  作者：Samkele Nsumiwa、David Kuter、Sergio Wittlin、Kelly Chibale、Timothy J. Egan

  DOI：10.1016/j.bmc.2013.04.040

  日期：2013.7

  In order to probe structure-activity relationships of association with ferriprotoporphyrin IX (logK) and inhibition of beta-hematin formation, a series of 4-aminoquinolines with varying substituents at the 7-position (X) have been synthesized. These have been further elaborated by introduction of two different R groups on the 4-amino nitrogen atom in the form of methyl (R = Me) and ethylamine (R = EtNH2) side chains. Data for a previously investigated series containing an N,N-diethyl-ethylamine side chain were also compared with the findings of this study. Experimentally, logK values for the simple 4-aminoquinoline series (R = H) were found to correlate with the hydrophobicity constant (pi) of the group X. The logK values for the series with R = Me and EtNH2 were found to correlate with those of the series with R = H. The log of the 50% beta-hematin inhibitory activity (log BHIA(50)) was found to correlate with logK and either meta (sigma(m)) or para (sigma(p)) Hammett constants for the series with R = Me and EtNH2, but not the simple series with R = H. To further improve predictability, correlations with ab initio electrostatic parameters, namely Mulliken and CHelpG charges were investigated. The best correlations were found with CHelpG charges which indicated that logK values can be predicted from the charges on atom H-8 and the group X in the quinolinium species computed in vacuum, while log BHIA50 values can be predicted from the CHelpG charges on C-7, C-8 and N-1 for the neutral species in vacuum. These correlations indicate that association and inhibition of beta-hematin formation are separately determined. They also suggest that electron withdrawing groups at the 7-position, but not necessarily hydrophobic groups are required for hemozoin inhibition. The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible. (C) 2013 Elsevier Ltd. All rights reserved.
• Structural Specificity of Chloroquine−Hematin Binding Related to Inhibition of Hematin Polymerization and Parasite Growth
  作者：Sudha Rani Vippagunta、Arnulf Dorn、Hugues Matile、Apurba K. Bhattacharjee、Jean M. Karle、William Y. Ellis、Robert G. Ridley、Jonathan L. Vennerstrom

  DOI：10.1021/jm9902180

  日期：1999.11.1

  Considerable data now support the! hypothesis that chloroquine (CQ)-hematin binding in the parasite food vacuole leads to inhibition of hemain polymerization and parasite death by hematin poisoning. To better understand the structural specificity of CQ-hematin binding, 13 CQ analogues were chosen and their hematin binding affinity, inhibition of hematin polymerization, and inhibition of parasite growth were measured. As determined by isothermal titration calorimetry (ITC-), the stoichiometry data and exothermic binding enthalpies indicated that, like CQ, these analogues bind to two or more hematin mu-oxo dimers in a cofacial pi-pi sandwich-type complex. Association constants (K-a's ranged from 0.46 to 2.9 x 10(5) M-1 compared to 4.0 x 10(5) M(-1)for CQ. Remarkably, we were not able to measure any significant interaction between hematin mu-oxo dimer and 11, the B-chloro analogue of CQ. This result indicates that the 7-chloro substituent in CQ is a critical structural determinant in its binding affinity to hematin mu-oxa dimer. Molecular modeling experiments reinforce the view that the enthalpically favorable pi-pi interaction observed in the CQ-hematin mu-oxo dimer complex derives from a favorable alignment of the out-of-plane pi-electron density in CQ and hematin Cc-ore dimer at the points of intermolecular contact. For 4-aminoquinolines related to CQ, our data suggest that, electron-withdrawing functional groups at the 7-position of the quinoline ring are required for activity against both hematin polymerization and parasite growth and that chlorine substitution at position 7 is optimal. Our results also confirm that the CQ diaminoalkyl side chain, especially the aliphatic tertiary nitrogen atom,is an important structural determinant in CQ drug resistance. For CQ analogues 1-13, the lack of correlation between K-a and hematin polymerization IC50 values suggests that other properties of the CQ-humatin mu-oxo dimer complex, rather than its association constant alone, play a role in the inhibition of hematin polymerization. However, there was a modest correlation between inhibition of hematin polymerization and inhibition of parasite growth when hematin polymerization IC50 values were normalized for hematin mu-oxo dimer binding affinities, adding further evidence that, antimalarial 4-aminoquinolines act by this mechanism.
• Nitro and amino substitution within the A-ring of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones: influence on topoisomerase I-targeting activity and cytotoxicity
  作者：Alexander L Ruchelman、John E Kerrigan、Tsai-Kun Li、Nai Zhou、Angela Liu、Leroy F Liu、Edmond J LaVoie

  DOI：10.1016/j.bmc.2004.03.076

  日期：2004.7

  Recently, 5H-8 9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h][1,6]naphthyridin-6-one, 1, was identified as a TOP1-targeting agent with pronounced antitumor activity. In the present study, the effect on activity of substituting, a single nitro or amino group in the A-ring in lieu of the methylenedioxy moiety of 1 was evaluated. The presence of either a nitro or amino substituent at the 4-position had a pronounced adverse affect on both TOP1-targeting activity and cytotoxicity. To a lesser extent, derivatives with a nitro or amino substituent at the 1-position were also less active than 1. Replacement of the methylenedioxy moiety of 1 with either a nitro or amino substituent at either the 2- and 3-position did result in analogues with potent TOP1-targeting activity and cytotoxicity. (C) 2004 Elsevier Ltd. All rights reserved.