丙二酸,[[(3-甲基苯基)氨基]亚甲基]-,二乙基酯 | 19056-83-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 丙二酸,[[(3-甲基苯基)氨基]亚甲基]-,二乙基酯
• 英文名称: diethyl 2-{[(3-methylphenyl)amino]methylene}propane-1,3-dioate
• 英文别名: diethyl 2-((m-tolylamino)methylene)malonate；diethyl 2-[((3-methylphenyl)amino)methylene]malonate；diethyl 2-[(3-toluidino)methylene]malonate；2-((m-tolylamino)methylene)malonic acid diethyl ester；(N-m-Tolyl-formimidoyl)-malonsaeure-diaethylester；m-toluidinomethylene-malonic acid diethyl ester；m-Toluidinomethylen-malonsaeure-diaethylester；m-Toluidinomethylen-malonsaeure-diethylester；Diethyl m-methylanilino-methylenmalonat；Diethyl 2-[(3-methylphenylamino)methylene]malonate；diethyl 2-[(3-methylanilino)methylidene]propanedioate
• CAS: 19056-83-8
• 化学式: C₁₅H₁₉NO₄
• 分子量: 277.32
• InChiKey: RSRNSQJGMCGUQB-UHFFFAOYSA-N

物化性质

• 熔点：
  39-40 °C(Solv: ethanol (64-17-5))
• 沸点：
  349.3±42.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  丙二酸,[[(3-甲基苯基)氨基]亚甲基]-,二乙基酯 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 1-ethyl-1,4-dihydro-7-methyl-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of Selected Novel Covalently Linked Flavoquinolones

  摘要：

  描述了通过混合酸酐法合成新型共价连接的黄酮喹诺酮类化合物，并通过紫外/可见光谱和1H核磁共振光谱数据进行了其光谱学研究。

  DOI：

  10.1055/s-2005-870019
• 作为产物：
  描述：

  3-硝基甲苯 在 铁粉 、 氯化铵 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 生成 丙二酸,[[(3-甲基苯基)氨基]亚甲基]-,二乙基酯
  参考文献：
  名称：

  Quinolone–Hydroxyquinoline Tautomerism in Quinolone 3-Esters. Preserving the 4-Oxoquinoline Structure To Retain Antimalarial Activity

  摘要：

  Recent publications report in vitro activity of quinolone 3-esters against the bc(1) protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silica at the yeast Q(o) Site established a key role for the 4-oxo and N-H groups in drug-target interactions. Thus, the possibility of 4-oxoquinoline/4-hydroxyquinoline tautomerism may impact in pharmacologic profiles and should be investigated. We describe the synthesis, structure, photochemistry, and activity against multidrug-resistant P. falciparum strain Dd2 of ethyl 4-oxo-7-methylquinoline-3-carboxylate (7Me-OQE) and ethyl 4-hydroxy-5-methylquinoline-3-carboxylate (5Me-HQE), obtained from diethyl 2-[((3-methylphenyl)amino)methylene]malonate. Theoretically (B3LYP/6-311+ +G(d,p)), 5Me-HQE and 7Me-OQE show clear preference for the hydroxyquinoline form. The difference between the lowest energy hydroxyquinoline and quinolone forms is 27 and 38 kJ mol(-1), for 5Me-HQE and 7Me-OQE, respectively. Calculations of atomaticity indexes show that in 5Me-HQE,both rings are aromatic, while in the corresponding oxo tautomers the nitrogen-containing ring is essentially non-aromatic. The structure of monomeric 5Me-HQE was studied using matrix-isolation coupled to FTIR spectroscopy. No traces of 4-oxoquinoline tautomers were found in the experimental IR spectra, revealing that:the species present in the crystal, 5Me-HQE center dot HCl, was lost HCl upon sublimation but did not tautomerize. Continuous broadband irradiation (lambda > 220 nm; 130 min) of the matrix led to only partial photodecomposition of 5Me-HQE (ca. 1/3).

  DOI：

  10.1021/acs.joc.5b02169

文献信息

• 3-(Benzo[<i>d</i>]thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase I inhibitor <i>via</i> DNA intercalation: design, synthesis, and antitumor activities
  作者：Jing-Mei Yuan、Nan-Ying Chen、Hao-Ran Liao、Guo-Hai Zhang、Xiao-Juan Li、Zi-Yu Gu、Cheng-Xue Pan、Dong-Liang Mo、Gui-Fa Su

  DOI：10.1039/c9nj05846j

  日期：——

  Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate

  已经设计并合成了二十七个3-（苯并[ d ]噻唑-2-基）-4-氨基喹啉衍生物作为拓扑异构酶I抑制剂。在体外针对四种人类肿瘤细胞系（MGC-803，人肝癌HepG-2，T24，和NCI-H460）和一个正常细胞系的抗增殖评价（HL-7702）表示，其中大部分表现出强的细胞毒性。其中，5a被认为是最有前途的候选物，其IC 50值低至约2.20±0.14，并被选作进一步探索。光谱分析和琼脂糖凝胶电泳分析表明5a可以与DNA相互作用并强烈抑制拓扑异构酶I（Topo I）。进一步筛选化合物5b的Topo I活性，5c，5e，5f，5h，5i，5j，5l和5n表明一些化合物可能与5a具有完全不同的细胞毒性。分子建模研究证实5a采用独特的模式与DNA和Topo I相互作用。其他分子机理研究表明，用5a处理MGC-803细胞可诱导S期阻滞，上调促凋亡蛋白，下调抗凋亡蛋白，激活caspase-3，随后诱导
• 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。
• A Clay Catalyzed Method For Diethyl 2,2,2-Trichloroethylidenepropanedioate, An Efficient Intermediate For The Synthesis Of Enamino Esters
  作者：A.R.A.S. Deshmukh、D. G. Panse、B. M. Bhawal

  DOI：10.1080/00397919908086168

  日期：1999.5

  Abstract An improved high yielding procedure for diethyl 2,2,2-trichloroethyledine-propanedioate (3) using montinorillonite K-10 catalyst has been described. Various diethyl (substituted aminomethylene)propanedioatcs (6a-j) have been synthesised in excellent yields starting from propanedioate (3) via addition products (5a-j).

  摘要 描述了使用蒙脱土 K-10 催化剂制备 2,2,2-三氯乙基丙二酸二乙酯 (3) 的改进高收率程序。从丙二酸酯 (3) 开始，通过加成产物 (5a-j)，已经以极好的收率合成了各种二乙基（取代氨基亚甲基）丙二酸酯 (6a-j)。
• 含氮杂环类化合物，及其制备方法、药物组合物和应用
  申请人：上海长森药业有限公司

  公开号：CN111039942B

  公开（公告）日：2023-04-14

  本发明提供了一种含氮杂环类化合物，及其制备方法、药物组合物和应用，具体地，本发明提供了一种如下式I所示的化合物，或其光学异构体、水合物、溶剂合物，或其药学上可接受的盐；其中，各基团的定义如说明书中所述。所述的式I化合物可以用于治疗与PD‑1/PD‑L1信号通路有关的疾病。
• Design, Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents
  作者：Chao Zhang、Yun-Sang Tang、Chu-Ren Meng、Jing Xu、De-Liang Zhang、Jian Wang、Er-Fang Huang、Pang-Chui Shaw、Chun Hu

  DOI：10.3390/ijms23116307

  日期：——

  4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay

  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