ethyl ester of 1-cyclopropyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acid | 127625-17-6

• 物质功能分类: 医药中间体 - 原料药中间体
• 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 ester of 1-cyclopropyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: ethyl 7-chloro-1-cyclopropylamino-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylate；ethyl 1-(cyclopropyl)-7-chloro-6-nitro-4-oxo-1,4-dihydro-quinoline-3-carboxylate；ethyl 1-cyclopropyl-7-chloro-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate；ethyl 7-chloro-1-cyclopropyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate；ethyl 7-chloro-1-cyclopropyl-6-nitro-4-oxoquinoline-3-carboxylate
• CAS: 127625-17-6
• 化学式: C₁₅H₁₃ClN₂O₅
• mdl: MFCD01088707
• 分子量: 336.732
• InChiKey: OKTIGDGVVZJJRI-UHFFFAOYSA-N

物化性质

• 熔点：
  >280 °C
• 沸点：
  518.5±50.0 °C(Predicted)
• 密度：
  1.531±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  ethyl ester of 1-cyclopropyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acid 在 盐酸 、 乙酸酐 、 tin(ll) chloride 作用下， 反应 4.83h， 生成 ethyl 7-chloro-1-cyclopropylamino-1,4-dihydro-6-formylamino-4-oxoquinoline-3-carboxylate
  参考文献：
  名称：

  Pyridonecarboxylic Acids as Antibacterial Agents. Part XVI. Imidazo- and Triazoloquinolones as Antibacterial Agents. Synthesis and Structure-Activity Relationships.

  摘要：

  合成了4, 5-二取代的6-环丙基-6, 9-二氢-9-氧代-1H-咪唑-(30-32)和三唑并[4, 5-f]喹啉-8-羧酸(33-35)从5, 6-二氨基喹诺酮25开始。咪唑并喹诺酮30-32的体外抗菌活性等于或优于相应的三唑并喹诺酮类似物33-35。至于C-5取代基，氟原子是H、F和Cl这三个基团中最有利的。在制备的化合物中，4-(环氨基)-5-氟-咪唑并喹诺酮31a-d对革兰氏阳性菌和革兰氏阴性菌均表现出有效且均衡的抗菌活性。还详细研究了 C-4 取代基（环状氨基）的结构-活性关系。

  DOI：

  10.1248/cpb.43.2123
• 作为产物：
  描述：

  ethyl ester of 3-dimethylamino-2-(5-nitro-2,4-dichlorobenzoyl)acrylic acid 在 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 生成 ethyl ester of 1-cyclopropyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  6-氨基喹诺酮类：一类新的喹诺酮类抗菌剂？

  摘要：

  通过先前的QSAR研究设计了一系列喹诺酮和1,8-萘啶酮-3-羧酸，它们的特征是在C-6位置的氨基而不是通常的氟原子，并进行了首次体外抗菌活性。所有合成的化合物都对革兰氏阴性菌保持良好的活性（铜绿假单胞菌除外），并且具有硫吗啉基作为C-7取代基的那些化合物也对革兰氏阳性菌具有良好的活性。还讨论了与C-1，C-5，C-7和C-8取代基相关的结构活性关系的某些方面。衍生物18g和38g对革兰氏阴性菌和革兰氏阳性菌分别具有0.45和0.66-0.76微克/ mL的几何平均MIC的最佳活性。这种抗菌活性反映了它们抑制细菌DNA旋转酶的能力。这项研究的结果表明，尽管C-6氟仍然是优选的取代基，但仍可通过用氨基取代而获得良好的活性。

  DOI：

  10.1021/jm00006a017

文献信息

• Advantageous Use of Ionic Liquids for the Synthesis of Pharmaceutically Relevant Quinolones
  作者：Rolando Cannalire、Matteo Tiecco、Violetta Cecchetti、Raimondo Germani、Giuseppe Manfroni

  DOI：10.1002/ejoc.201800415

  日期：2018.6.22

  The use of ILs instead of DMF in the Grohe cycloaracylation for the synthesis of pharmaceutically relevant quinolones has several advantages. [TBMA][MsO] was the most favourable IL and was used in a one‐pot/three‐step procedure for the preparation of a quinolone acid by a totally green procedure. Our procedure represents an alternative approach to the industrial production of quinolones.

  在Grohe环酰化反应中使用IL代替DMF合成药物相关喹诺酮具有若干优势。[TBMA] [MsO]是最有利的IL，用于一锅/三步程序中，通过完全绿色的程序制备喹诺酮酸。我们的程序代表了喹诺酮类工业生产的替代方法。
• From 6-Aminoquinolone Antibacterials to 6-Amino-7-thiopyranopyridinylquinolone Ethyl Esters as Inhibitors of <i>Staphylococcus aureus</i> Multidrug Efflux Pumps
  作者：Marco Pieroni、Mirjana Dimovska、Jean Pierre Brincat、Stefano Sabatini、Emanuele Carosati、Serena Massari、Glenn W. Kaatz、Arnaldo Fravolini

  DOI：10.1021/jm1003304

  日期：2010.6.10

  poor substrates for NorA was investigated further. Several quinolone ester intermediates, devoid of any intrinsic antibacterial activity, were tested for their abilities to inhibit the activities of NorA (MFS family) and MepA (MATE family) S. aureus MDR efflux pumps. Selected quinolone esters were capable of inhibiting both MDR pumps more efficiently than the reference compound reserpine. Moreover, they

  硫代吡喃吡啶部分被合成为新的杂环碱基，插入选定的喹诺酮核的C-7位置，然后确定对金黄色葡萄球菌菌株的抗菌活性。选定的硫吡喃并吡啶基喹诺酮类药物显示出显着的抗菌活性，包括在gyrA和grlA中具有突变的菌株以及其他过表达NorA多药（MDR）外排泵的菌株。大多数衍生物似乎不是NorA底物。进一步研究了硫代吡喃并吡啶基取代基使这些喹诺酮类药物成为NorA不良底物的作用。测试了几种不含任何固有抗菌活性的喹诺酮酯中间体抑制NorA（MFS家族）和MepA（MATE家族）金黄色葡萄球菌MDR外排泵的活性。与参考化合物利血平相比，所选的喹诺酮酯能够更有效地抑制两种MDR泵。而且，它们还能够恢复甚至增强环丙沙星对某些基因修饰的抗金黄色葡萄球菌菌株的活性。
• Novel synthesis of 3-nitro-4-quinolone derivatives
  作者：M. M. Maslova、N. B. Marchenko、V. I. Po1'shakov、R. G. Glushkov

  DOI：10.1007/bf00781074

  日期：1993.2

  the selective introduction of the nitro group into ~-electron-deficient nitrogen heterocycles has not been clearly resolved to date. This circumstance makes the task of developing preparative methods for the synthesis of 3-nitro-4-quinolones a vital one, as it has been previously. 3-Nitroquinoline derivatives are of interest for pharmacological research as potential drugs and also as convenient key

  将硝基选择性引入到缺电子氮杂环中的问题迄今尚未得到明确解决。这种情况使得开发用于合成 3-硝基-4-喹诺酮类的制备方法的任务成为一项至关重要的任务，就像以前一样。3-硝基喹啉衍生物作为潜在的药物和用于制备生物活性化合物的方便的关键产品在药理学研究中很受关注。
• 6-Aminoquinolones as New Potential Anti-HIV Agents
  作者：Violetta Cecchetti、Cristina Parolin、Stefano Moro、Teresa Pecere、Enrica Filipponi、Arianna Calistri、Oriana Tabarrini、Barbara Gatto、Manlio Palumbo、Arnaldo Fravolini、Giorgio Palu’

  DOI：10.1021/jm9903390

  日期：2000.10.1

  A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC50 value was 0.1 mu M, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.
• Synthesis and antimycobacterial activities of novel 6-nitroquinolone-3-carboxylic acids
  作者：Palaniappan Senthilkumar、Murugesan Dinakaran、Perumal Yogeeswari、Dharmarajan Sriram、Arnab China、Valakunja Nagaraja

  DOI：10.1016/j.ejmech.2008.02.031

  日期：2009.1

  Various 1-(substituted)-1,4-dihydro-6-nitro-4-oxo-7-(sub-secondary amino)-quinoline-3-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid by six step synthesis. The compounds were evaluated for antimycobacterial in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the 48 synthesized compounds, 7-(4-((benzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-1-cyclopropyl-1,4-dihydro-6-nitro-4-oxoquinotine-3-carboxylic acid (8c) was found to be the most active compound in vitro with MIC of 0.08 and 0.16 mu M against MTB and MDR-TB, respectively. In the in vivo animal model 8c decreased the bacterial load in lung and spleen tissues with 2.78 and 4.15-log 10 protections, respectively, at the dose of 50 mg/kg body weight. (C) 2008 Elsevier Masson SAS. All rights reserved.