diethyl 2-((2,4-difluorophenylamino)methylene)malonate | 101830-90-4

• 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: diethyl 2-((2,4-difluorophenylamino)methylene)malonate
• 英文别名: Diethyl 2-[(2,4-difluoroanilino)methylene]malonate；diethyl 2-[(2,4-difluoroanilino)methylidene]propanedioate
• CAS: 101830-90-4
• 化学式: C₁₄H₁₅F₂NO₄
• 分子量: 299.274
• InChiKey: ZVPNJCJOCQTWNB-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：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-((2,4-difluorophenylamino)methylene)malonate 以 二苯醚 为溶剂， 反应 1.0h， 生成 6,8-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

  摘要：

  A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV-vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b-DNA complex which might block DNA replication and thus exert its antimicrobial activities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.118
• 作为产物：
  描述：

  丙二酸二乙酯 在 乙酸酐 、 zinc(II) chloride 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 diethyl 2-((2,4-difluorophenylamino)methylene)malonate
  参考文献：
  名称：

  Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

  摘要：

  A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV-vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b-DNA complex which might block DNA replication and thus exert its antimicrobial activities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.118

文献信息

• Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs
  作者：Davide Carta、Paola Brun、Matteo Dal Pra、Giulia Bernabè、Ignazio Castagliuolo、Maria Grazia Ferlin

  DOI：10.1039/c8md00139a

  日期：——

  new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant Staphylococcus aureus. Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the

  我们的目标是确定具有抗炎和抗菌活性的新的多靶点化合物，用于治疗人类感染。Diflunisal 是一种非甾体抗炎剂，最近因其对耐甲氧西林金黄色葡萄球菌的抗毒力特性而被重新利用。抗炎药二氟尼柳的一些氮杂类似物的有效合成是按照关键恶唑中间体的路线进行的，以获得o-和m-羟基吡啶羧酸衍生物。新合成的二氟尼柳氮杂类似物在高达 80 μM 时没有表现出细胞毒活性，其中一些表现出抗炎活性，降低了人原代巨噬细胞中细菌脂多糖诱导的促炎细胞因子和前列腺素的水平。发现 10 种二氟尼柳氮杂类似物具有有趣的抗菌活性，使金黄色葡萄球菌、化脓性链球菌、屎肠球菌和铜绿假单胞菌对 β-内酰胺类抗生素和蛋白质合成抑制剂的抗菌作用敏感。
• Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat–TAR interaction inhibitors
  作者：Shuguang Chen、Ran Chen、Meizi He、Ruifang Pang、Zhiwu Tan、Ming Yang

  DOI：10.1016/j.bmc.2009.01.038

  日期：2009.3

  Thirty-two quinoline derivatives were designed and synthesized as HIV-1 Tat–TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Nine of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells, indicating effective inhibitory

  设计并合成了32种喹啉衍生物作为HIV-1 Tat-TAR相互作用抑制剂。所有这些化合物在抑制CEM174细胞中SIV诱导的合胞体形成方面均表现出很高的抗病毒活性。在人的293T细胞中，通过Tat依赖HIV-1 LTR驱动的CAT基因表达比色酶分析评估了其中9种低细胞毒性，表明它们具有有效的抑制Tat-TAR相互作用的抑制活性。分子模拟实验表明，这些化合物可能通过与Tat蛋白而非TAR RNA结合而抑制Tat-TAR相互作用。
• Antibacterial Activity of 6, 8-Disubstituted-Quinolone-3-Carboxylic Acids
  作者：Raghavan Krishnan、S.A. Lang

  DOI：10.1002/jps.2600751214

  日期：1986.12

  Twelve 6,8-disubstituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid derivatives were prepared and evaluated for their antibacterial activity. Among these, only the 6,8-difluoroquinolinone-3-carboxylic acid showed moderate activity.

  制备了十二种6,8-二取代-1-乙基-1,4-二氢-4-氧代喹啉-3-羧酸衍生物，并对其抗菌活性进行了评估。其中，仅6,8-二氟喹啉酮-3-羧酸显示中等活性。
• Quinoline derivatives, their preparation and therapeutic compositions
  申请人：Societe de Conseils de Recherches et d'Applications Scientifiques

  公开号：US04914110A1

  公开（公告）日：1990-04-03

  The invention relates to new quinoline derivatives of the formula: ##STR1## wherein R stands for C.sub.2 H.sub.5, C.sub.2 H.sub.4 F, CH.sub.2 -O-CH.sub.2 -CH.sub.2 OH, ##STR2## to a process for their preparation comprising reacting, for 12-24 hours, at 70.degree.-95.degree. C., in dimethylformamide, the 1,4-dihydro- 3-ethoxycarbonyl- 6,8- difluoro-4-oxo-quinoline with an excess of RX (2-5 mol of RX for one mol of quinoline), in the presence of K.sub.2 CO.sub.3 and subsequently hydrolysing the obtained 3-ester by HCl under reflux conditions and to pharmaceutical compositions comprising at least one 1,4-dihydro- 3-carboxy- 6,8-difluoro- 1-R-4-oxo-quinoline derivative in admixture with a pharmaceutically acceptable diluent or carrier.

  本发明涉及一种新的喹啉衍生物的公式：##STR1##其中R代表C.sub.2 H.sub.5，C.sub.2 H.sub.4 F，CH.sub.2-O-CH.sub.2-CH.sub.2 OH，##STR2##以及一种制备它们的方法，包括在二甲基甲酰胺中，在70℃至95℃下与过量的RX（对于一摩尔喹啉，2-5摩尔RX）在K.sub.2 CO.sub.3的存在下反应12-24小时，然后在回流条件下通过HCl水解所得到的3-酯，以及包含至少一种1,4-二氢-3-羧基-6,8-二氟-1-R-4-酮-喹啉衍生物的制药组合物，与药用可接受的稀释剂或载体混合。
• New quinoline derivatives, their preparation and therapeutic
  申请人：Societe de Conseils de Recherches et d'Applications Scientifiques

  公开号：US04782068A1

  公开（公告）日：1988-11-01

  The invention relates to new quinoline derivatives of the formula: ##STR1## wherein R stands for C.sub.2 H.sub.5, C.sub.2 H.sub.4 F, CH.sub.2 --O--CH.sub.2 --CH.sub.2 OH, ##STR2## to a process for their preparation comprising reacting, for 12-24 hours, at 70.degree.-95.degree. C., in dimethylformamide, the 1,4-dihydro- 3-ethoxycarbonyl- 6,8- difluoro-4-oxo-quinoline with an excess of RX (2-5 mol of RX for one mol of quinoline), in the presence of K.sub.2 CO.sub.3 and subsequently hydrolyzing the obtained 3-ester by HCl under reflux conditions and to pharmaceutical compositions comprising at least one 1,4-dihydro- 3-carboxy- 6,8-difluoro- 1-R-4-oxo-quinoline derivative in admixture with a pharmaceutically acceptable diluent or carrier.

  本发明涉及以下式的新喹啉衍生物： ##STR1## 其中R代表C.sub.2 H.sub.5，C.sub.2 H.sub.4 F，CH.sub.2 --O--CH.sub.2 --CH.sub.2 OH， ##STR2## 以及它们的制备方法，包括在二甲基甲酰胺中，在70℃至95℃下，反应12-24小时，用过量的RX（2-5摩尔的RX对于1摩尔的喹啉）在K.sub.2 CO.sub.3的存在下与1,4-二氢-3-乙酰氧基-6,8-二氟-4-氧代喹啉反应，随后在回流条件下通过HCl水解所得的3-酯，并且还涉及含有至少一种1,4-二氢-3-羧基-6,8-二氟-1-R-4-氧代喹啉衍生物的制药组合物，与药学可接受的稀释剂或载体混合。