ethyl 6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylate | 26892-93-3

• 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
• 英文名称: ethyl 6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: Ethyl 6,7-dichloro-4-hydroxyquinoline-3-carboxylate；ethyl 6,7-dichloro-4-oxo-1H-quinoline-3-carboxylate
• CAS: 26892-93-3；122224-58-2
• 化学式: C₁₂H₉Cl₂NO₃
• 分子量: 286.114
• InChiKey: PMGNGTDFPXCYNP-UHFFFAOYSA-N

物化性质

• 沸点：
  398.4±37.0 °C(Predicted)
• 密度：
  1.478±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  ethyl 6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 盐酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 6,7-dichloro-1-ethyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  使用多糖负载的铜纳米粒子通过ipso硝化将 3-羧基-4-喹诺酮类转化为3-硝基-4-喹诺酮类：合成3-羧基-4-喹诺酮类的3-四唑基生物同工异构体作为抗菌剂†

  摘要：

  壳聚糖负载的Cu纳米粒子已经合成，并用于通过ipso硝化反应从3-羧基-4-喹诺酮类化合物合成3-硝基-4-喹诺酮类化合物。与标准环丙沙星相比，4-喹诺酮的合成3-硝基衍生物已成功转化为3-四唑基生物甾醇，其抗菌活性增强。

  DOI：

  10.1039/c5ra26909a
• 作为产物：
  描述：

  diethyl 2-(((3,4 -dichlorophenyl)amino)methylene)malonate 以 二苯醚 为溶剂， 生成 ethyl 6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  通过ipso硝化作用 将3-羧基-4-喹诺酮类药物有效转化为3-硝基-4-喹诺酮类药物：潜在的抗丝虫剂可作为马来酸胸腺嘧啶激酶的抑制剂†

  摘要：

  通过在水中定量使用乙酸铜和硝酸银，已经开发了一种高效，经济，绿色的ipso硝化方法，用于合成3-羧基4-喹诺酮的3-硝基衍生物。DFT计算解释了观察到的硝化区域选择性。这些化合物中的三种对马来酸胸腺嘧啶激酶的IC 50值为（2.9–3.4μmol），可能是良好的抗丝虫剂，这也通过分子对接研究得到了证明。

  DOI：

  10.1039/c5ra18036h

文献信息

• One-Pot Approach to Pyrido-4-phenanthridinones by Palladium-Catalyzed Annulation of 4-Quinolones with 2-Bromobenzyl Bromides
  作者：Athar Ata、Palathurai Mohan、Thangaraj Arasakumar、Selvaraj Shyamsivappan、Subashini Gopalan

  DOI：10.1055/s-0037-1610333

  日期：2019.1

  A straightforward approach toward the assembly of phenanthridinone heterocycles has been developed through the palladium-catalyzed N-benzylation/intramolecular coupling reactions of readily prepared 4-quinolones with commercially available 2-bromobenzyl bromide derivatives. The target products were prepared in moderate to good yields, with tolerance of various functional groups.

  已经通过钯催化的N-苄基化/分子内偶联反应的直接方法，成功地组装了苯并喹啉酮杂环。该方法利用易于制备的4-喹啉酮与市售2-溴苄溴衍生物进行反应，产物收率在中等到良好之间，并且对各种官能团具有一定的耐受性。
• Design, Synthesis, SAR, Pharmacokinetic Prediction of New 4-Quinolones as Anti-Microbial Agents
  作者：G. G. Dubal、P. R. Vachchharajani、M. J. Solanki、V. H. Shah

  DOI：10.1134/s1070363222100280

  日期：2022.10

  Abstract s of new 4-quinolone derivatives was synthesized by conventional heating method. For the synthesized compounds, we performed pharmacokinetic prediction, SAR and antimicrobial assay. The presence of halogen elements plays a key role in the biological activity that is clear by in vitro analysis. Target compounds exhibit moderate to significant activity near to standard marketed drugs like amoxycillin

  摘要 采用常规加热方法合成了新型4-喹诺酮衍生物。对于合成的化合物，我们进行了药代动力学预测、SAR 和抗菌测定。卤族元素的存在在生物活性中起着关键作用，这一点通过体外分析已明确。目标化合物表现出接近标准市售药物（如阿莫西林、氯霉素、环丙沙星、诺氟沙星、灰黄霉素和制霉菌素）的中度至显着活性。
• Lead Optimization of 3-Carboxyl-4(1<i>H</i>)-Quinolones to Deliver Orally Bioavailable Antimalarials
  作者：Yiqun Zhang、Julie A. Clark、Michele C. Connelly、Fangyi Zhu、Jaeki Min、W. Armand Guiguemde、Anupam Pradhan、Lalitha Iyer、Anna Furimsky、Jason Gow、Toufan Parman、Farah El Mazouni、Margaret A. Phillips、Dennis E. Kyle、Jon Mirsalis、R. Kiplin Guy

  DOI：10.1021/jm201642z

  日期：2012.5.10

  Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.
• An NMR Study of Halogenated 1,4-Dihydro-1-ethyl-4-oxoquinoline-3-carboxylates
  作者：B. Podányi、G. Keresztúri、L. Vasvári-Debreczy、I. Hermecz、G. Tóth

  DOI：10.1002/(sici)1097-458x(199611)34:11<972::aid-omr994>3.0.co;2-9

  日期：1996.11

  Ethyl 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylate and 29 of its mono-, di- and tri-fluoro and/or -chloro derivatives were synthesized and their H-1, C-13 and F-19 NMR spectra were recorded. H-1,C-13 and F-19 chemical shifts, J(HH), J(FH), J(CF) and J(FF) coupling constants are reported. The C-13 substituent chemical shift values of the chloro and fluoro substituents were calculated by linear multiple regression.
• Quinolone Nucleosides: 6,7-Dihalo-N-β- and α-Glycosyl-l 4-dihydro-4-oxo-quinoline-3-carboxylic Acids and Derivatives. Synthesis, Antimicrobial and Antiviral Activity
  作者：Najim A. Al-Masoudi、Yaseen A. Al-Soud、Micheal Ehrmann、Erik de Clercq

  DOI：10.1080/07328319808004315

  日期：1998.12

  Reaction of the silylated 6,7-dihaloquinoline bases 10-12 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (13) gave ethyl 7-chloro-6-flouro-1,4-dihydro-4-oxo-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)quinoline-3-carboxylate (14) and the free acids 15 and 16, respectively, which led on deblocking of the sugar moiety to the free nucleosides 17, 18 and 20, respectively. Treatment of 14 with methanolic ammonia afforded the amide derivative 19. Ribosylation of 11 with 1,2-di-O-acetyl-3-azido-3-deoxy-5-p-toluoyl-beta-D-ribofuranose (21) afforded the azido nucleoside 22, which was again converted into the free nucleoside 23. Analogously, reaction of 11 with the chloro deoxyribose derivative 24 led to a mixture of alpha / beta (2:1) anomers of 25. Deblocking and recrystallization of the product gave mainly the alpha-anomer 26. Compounds 17-19, 23 and 26 were evaluated against Escherichia coli and found inactive. Compound 16-18 and 22 were inactive aganist HIV-1 (III B) and HIV-2 (ROD) induced cytopathicity in human MT-4 lymphocyte cells.