7-甲基-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 | 77721-00-7

• 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-甲基-4-氧代-1,4-二氢喹啉-3-羧酸乙酯
• 英文名称: ethyl 7-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 7-methyl-4-oxo-1H-quinoline-3-carboxylate
• CAS: 77721-00-7
• 化学式: C₁₃H₁₃NO₃
• 分子量: 231.251
• InChiKey: OZOMNKPYBWQMAH-UHFFFAOYSA-N

物化性质

• 沸点：
  365.5±42.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-甲基-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 在 水 、 sodium hydroxide 、 三氯氧磷 作用下， 以 二苯醚 为溶剂， 反应 7.8h， 生成 4-氯-7-甲基喹啉
  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：

  3-硝基甲苯 在 铁粉 、 氯化铵 作用下， 以 甲醇 、 水 为溶剂， 反应 7.0h， 生成 7-甲基-4-氧代-1,4-二氢喹啉-3-羧酸乙酯
  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

• Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs
  申请人：3M Innovative Properties Company

  公开号：US06110929A1

  公开（公告）日：2000-08-29

  Thiazolo-, oxazolo- and selenazolo[4,5-c]quinolin-4-amines and analogs thereof are described including methods of manufacture and the use of novel intermediates. The compounds are immunomodulators and induce cytokine biosynthesis, including interferon and/or tumor biosynthesis, necrosis factor, and inhibit the T-helper-type 2 immune response. The compounds are further useful in the treatment of viral and neoplastic diseases.

  Thiazolo-, oxazolo-和selenazolo[4,5-c]quinolin-4-胺及其类似物的描述包括制造方法和新型中间体的使用。这些化合物是免疫调节剂，能诱导细胞因子生物合成，包括干扰素和/或肿瘤生物合成、坏死因子，并抑制T辅助型2型免疫应答。这些化合物在治疗病毒性和肿瘤性疾病方面也很有用。
• Synthesis of Selected Novel Covalently Linked Flavoquinolones
  作者：Ram Singh、Geetanjali

  DOI：10.1055/s-2005-870019

  日期：——

  The synthesis of novel covalently linked flavoquino­lones via amide bond is described using mixed anhydride method and their spectroscopic studies have been done by UV/Vis and 1H NMR spectroscopic data.

  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。
• 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
• 4-hydroxyquinoline-3-carboxamides and hydrazides as antiviral agents
  申请人：Pharmacia & Upjohn Company

  公开号：US06093732A1

  公开（公告）日：2000-07-25

  The present invention provides 4-hydroxyquinoline-3-carboxamide and hydrazide compounds of formula I ##STR1## These compounds are useful to treat or prevent the herpesviral infections, particularly, human cytomegaloviral infection.

  本发明提供了式I的4-羟基喹啉-3-甲酰胺和肼化合物。这些化合物可用于治疗或预防疱疹病毒感染，特别是人类巨细胞病毒感染。
• Antiviral Activity of 4-Oxoquinoline-3 - Carboxamide Derivatives against Bovine Herpesvirus Type 5
  作者：Ana Maria V Pinto、José Paulo G Leite、Robson SS Marinho、Luana da SM Forezi、Pedro N Batalha、Fernanda da CS Boechat、Anna C Cunha、David O Silva、Ivson L Gama、Letícia V Faro、Maria CBV de Souza、Izabel Christina P Paixão

  DOI：10.3851/imp3329

  日期：2020.1

  Bovine herpesvirus type 5 is an important agent of meningoencephalitis in cattle and has been identified in outbreaks of bovine neurological disease in several Brazilian states. In recent years, oxoquinoline derivatives have become an important focus in antiviral drug research.

  The cytotoxicity and anti BoHV-5RJ42/01 activity of a set of synthetic 4-oxoquinoline derivatives 4a-k were assayed on Madin–Darby Bovine Kidney cell and antiviral activity by plaque reduction assay. Results: The most promising substance (4h) exhibited CC₅₀and EC₅₀values of 1,239 μM ±5.5 and 6.0 μM ±1.5, respectively, with an SI =206. Two other compounds 4j (CC₅₀= 35 μM ±2 and EC₅₀= 24 μM ±7.0) and 4k (CC₅₀= 55 μM ±2 and EC₅₀= 24 μM ±5.1) presented similar inhibitory profile and selectivity indexes of 1.4 and 2.9, respectively. The results of the time-of-addition studies revealed expressive reduction of virus production (≥80%) in different stages of virus replication cycle except for compound 4h that slightly inhibited virus yield in the first 2 h post infection, but it showed expressive virus inhibition after this time.

  All three compounds slightly interact with the virus on the virucidal assay and they are not able to block virus attachment and penetration. Antiviral effect of oxoquinoline 4h was more prominent than acyclovir which leads us to suggest compound 4h as a promising molecule for further anti-BoHV-5 drug design.

  背景牛疱疹病毒 5 型是牛脑膜脑炎的重要病原体，已在巴西多个州爆发的牛神经系统疾病中被发现。近年来，氧化喹啉衍生物已成为抗病毒药物研究的一个重点。方法在麦丁达比牛肾细胞上检测了一组合成的 4-oxoquinoline 衍生物 4a-k 的细胞毒性和抗 BoHV-5RJ42/01 活性，并通过斑块还原试验检测了其抗病毒活性。结果：最有希望的物质（4h）的 CC50 和 EC50 值分别为 1,239 μM ±5.5 和 6.0 μM ±1.5，SI =206。另外两种化合物 4j（CC50= 35 μM ±2，EC50= 24 μM ±7.0）和 4k（CC50= 55 μM ±2，EC50= 24 μM ±5.1）具有相似的抑制作用，选择性指数分别为 1.4 和 2.9。添加时间的研究结果表明，在病毒复制周期的不同阶段，除了化合物 4h 在感染后的前 2 h 稍微抑制了病毒产量外，其他化合物都明显减少了病毒产量（≥80%）。氧化喹啉 4h 的抗病毒效果比阿昔洛韦更突出，因此我们建议将化合物 4h 作为进一步设计抗 BoHV-5 药物的理想分子。