2,2-dimethyl-5-((3-nitrophenylamino)methylene)-1,3-dioxane-4,6-dione | 25063-48-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,2-dimethyl-5-((3-nitrophenylamino)methylene)-1,3-dioxane-4,6-dione
• 英文别名: GC04；2,2-Dimethyl-5-[(3-nitroanilino)methylene]-1,3-dioxane-4,6-dione；2,2-dimethyl-5-[(3-nitroanilino)methylidene]-1,3-dioxane-4,6-dione
• CAS: 25063-48-3
• 化学式: C₁₃H₁₂N₂O₆
• 分子量: 292.248
• InChiKey: BOFJWFRJCGVZKD-UHFFFAOYSA-N

物化性质

• 熔点：
  217 °C
• 沸点：
  516.0±50.0 °C(Predicted)
• 密度：
  1.488±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-5-((3-nitrophenylamino)methylene)-1,3-dioxane-4,6-dione 在 三氯氧磷 作用下， 以 二苯醚 为溶剂， 反应 0.5h， 生成 4-氯-7-硝基喹啉
  参考文献：
  名称：

  Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.04.040
• 作为产物：
  描述：

  5-乙氧基甲烯基-2,2-二甲基-1,3-二氧六环-4,6-二酮 、 间硝基苯胺 以 乙醇 为溶剂， 以84.5%的产率得到2,2-dimethyl-5-((3-nitrophenylamino)methylene)-1,3-dioxane-4,6-dione
  参考文献：
  名称：

  外来氨基酸。8. N-芳基氨基亚甲基丙二酸单甲基酯的合成

  摘要：

  DOI：

  10.1023/a:1020641922707

文献信息

• Synthesis and biological evaluation of new heterocyclic quinolinones as anti-parasite and anti-HIV drug candidates
  作者：Albert Darque、Aurélien Dumètre、Sébastien Hutter、Gilles Casano、Maxime Robin、Christophe Pannecouque、Nadine Azas

  DOI：10.1016/j.bmcl.2009.08.013

  日期：2009.10

  We have synthesized quinolinones with potential antiparasitic and anti-HIV activities by an original two-step method involving microwave irradiation and have evaluated their activities against Plasmodium falciparum, Leishmania donovani, Trichomonas vaginalis, and HIV. None of the tested compounds had been previously described using this method of synthesis. One of the compounds had interesting antiparasitic

  我们已经通过涉及微波辐射的原始两步法合成了具有潜在抗寄生虫和抗HIV活性的喹啉酮，并评估了它们对恶性疟原虫，杜氏利什曼原虫，阴道毛滴虫和HIV的活性。以前没有使用这种合成方法描述过测试化合物。其中一种化合物具有令人感兴趣的抗寄生虫和抗HIV活性，可以通过用不同的基团取代来提高其活性。
• Gas-Phase Pyrolysis in Organic Synthesis: Rapid Green Synthesis of 4-Quinolinones
  作者：Nouria Al-Awadi、Ismail Abdelhamid、Ismail Abdelhamid、Alya Al-Etaibi、Mohamed Elngadi

  DOI：10.1055/s-2007-985573

  日期：——

  Gas-phase pyrolysis of aminomethylene Meldrum’s acid derivatives gave quinolinones and/or amines depending on the -nature of arylamino moiety. Effect of substituent on reaction rate and nature of pyrolysis products supports the suggested intramolecular nucleophilic substitution reaction via initially formed keteneamine intermediate.

  根据芳基氨基部分的性质，氨基亚甲基 Meldrum 的酸衍生物的气相热解得到喹啉酮和/或胺。取代基对反应速率和热解产物性质的影响支持通过最初形成的烯酮胺中间体进行的分子内亲核取代反应。
• Synthesis and pharmacological evaluation of new cysLT1 receptor antagonists
  作者：R Griera、M Armengol、A Reyes、M Alvarez、A Palomer、F Cabré、J Pascual、M.L. Garcia、D Mauleón

  DOI：10.1016/s0223-5234(97)83282-5

  日期：1997.7

  This paper describes the synthesis and pharmacological evaluation of three series of compounds 4a-b, 13a-k and 19, structurally related to the known potent cysLT(1) receptor antagonists RG-12553, ICI-204219 and ONO-1078, respectively. The common structural feature of these new series is the presence of a 4-quinolone nucleus acting as a template for substitution of the aromatic nucleus present in the prototype antagonists. We describe the evolution of these series leading to antagonists with potency at nanomolar concentrations in vitro.
• 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.
• ——
  作者：D. Zicane、I. Ravina、Z. Tetere、I. Rijkure、M. Petrova、U. Kalejs

  DOI：10.1023/a:1020641922707

  日期：——