ethyl ester of 3-dimethylamino-2-(5-nitro-2,4-dichlorobenzoyl)acrylic acid | 148926-94-7

• 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: ethyl ester of 3-dimethylamino-2-(5-nitro-2,4-dichlorobenzoyl)acrylic acid
• 英文别名: ethyl 2-(2,4-dichloro-5-nitrobenzoyl)-3-(dimethylamino)acrylate；Ethyl 2-(2,4-dichloro-5-nitrobenzoyl)-3-(dimethylamino)prop-2-enoate
• CAS: 148926-94-7
• 化学式: C₁₄H₁₄Cl₂N₂O₅
• 分子量: 361.182
• InChiKey: VAGGYVYRJORKFY-UHFFFAOYSA-N

物化性质

• 沸点：
  487.8±45.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 2.25h， 生成 Ethyl 7-(2-aminoethylsulfanyl)-1-cyclopropyl-6-nitro-4-oxoquinoline-3-carboxylate
  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
• 作为产物：
  描述：

  2,4-dichloro-5-nitro benzoyl chloride 反应 5.0h， 生成 ethyl ester of 3-dimethylamino-2-(5-nitro-2,4-dichlorobenzoyl)acrylic acid
  参考文献：
  名称：

  Synthesis and amination of 1-alkyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acids

  摘要：

  DOI：

  10.1007/bf02464110

文献信息

• Studies of Anti-HIV Transcription Inhibitor Quinolones: Identification of Potent N1-Vinyl Derivatives
  作者：Oriana Tabarrini、Serena Massari、Dirk Daelemans、Francesco Meschini、Giuseppe Manfroni、Laura Bottega、Barbara Gatto、Manlio Palumbo、Christophe Pannecouque、Violetta Cecchetti

  DOI：10.1002/cmdc.201000267

  日期：2010.11.8

  Tat‐mediated transcription. This particular mechanism of action makes this class of compounds very attractive for further structural investigations. Identification of the pharmacophore required for inhibition will ultimately result in the design of more selective analogues for use in combination therapy for the treatment of HIV infections. We have focused on the pyridone ring of the quinolone nucleus present

  6-去氟喹诺酮类药物（6-DFQs）是针对Tat介导的转录的抗HIV药物。这种特殊的作用机理使这类化合物对于进一步的结构研究非常有吸引力。抑制所需药效基团的鉴定最终将导致设计出更具选择性的类似物，以用于治疗HIV感染的联合疗法。我们集中研究了这些化合物中存在的喹诺酮核的吡啶酮环，设计了新的修饰方法以拓宽结构与活性之间的关系知识库。在此，我们介绍了新型且非常有效的抗HIV喹诺酮类药物，最值得注意的是在N1位带有氨基或乙烯基的喹诺酮类药物。试图确定赋予乙烯基衍生物有效的抗HIV活性所必需的结构参数。
• 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.
• Ethyl 1,8-Naphthyridone-3-carboxylates Downregulate Human Papillomavirus-16 E6 and E7 Oncogene Expression
  作者：Manuela Donalisio、Serena Massari、Monica Argenziano、Giuseppe Manfroni、Valeria Cagno、Andrea Civra、Stefano Sabatini、Violetta Cecchetti、Arianna Loregian、Roberta Cavalli、David Lembo、Oriana Tabarrini

  DOI：10.1021/jm500340h

  日期：2014.7.10

  Strong epidemiological and molecular data associate cervical cancer (CC) with high-risk human papillomavirus (HPV) infections. The carcinogenic mechanism depends mainly on the expression of E6 and E7 oncoproteins encoded by the viral genome. Using a cell-based high-throughput assay, an in-house library of compounds was screened identifying the 1,8-naphthyridone 1 that efficiently inhibited the transcription driven by the long control region of the HPV genome. A series of analogues were then synthesized, obtaining more potent derivatives able to downregulate E6 and E7 transcripts in HPV-16-positive CC CaSki cells. An unusual structural insight emerged for the C-3 position of the 1,8-naphthyridone core, where the ethyl carboxylate esters, but not the carboxylic acids, are responsible for the activity. In vitro uptake studies showed that the 3-ethyl carboxylates do not act as prodrugs. The 1,8-naphthyridones emerged as valid starting points for the development of innovative agents potentially useful for the treatment of HPV-induced CC.
• The Versatile Nature of the 6-Aminoquinolone Scaffold: Identification of Submicromolar Hepatitis C Virus NS5B Inhibitors
  作者：Giuseppe Manfroni、Rolando Cannalire、Maria Letizia Barreca、Neerja Kaushik-Basu、Pieter Leyssen、Johan Winquist、Nunzio Iraci、Dinesh Manvar、Jan Paeshuyse、Rupa Guhamazumder、Amartya Basu、Stefano Sabatini、Oriana Tabarrini、U. Helena Danielson、Johan Neyts、Violetta Cecchetti

  DOI：10.1021/jm401362f

  日期：2014.3.13

  We have previously reported that the 6-aminoquinolone chemotype is a privileged scaffold to obtain antibacterial and antiviral agents. Herein we describe the design, synthesis, and enzymatic and cellular characterization of new 6-aminoquinolone derivatives as potent inhibitors of NS5B polymerase, an attractive and viable therapeutic target to develop safe anti-HCV agents. The 6-amino-7-[4-(2-pyridinyl)-1-piperazinyl]quinolone derivative 8 proved to be the best compound of this series, exhibiting an IC50 value of 0.069 mu M against NS5B polymerase and selective antiviral effect (EC50 = 3.03 mu M) coupled with the absence of any cytostatic effect (CC50 > 163 mu M; SI > 54) in Huh 9-13 cells carrying a HCV genotype 1b, as measured by MTS assay. These results indicate that the 6-aminoquinolone scaffold is worthy of further investigation in the context of NS5B-targeted HCV drug discovery programs.
• Synthesis of 1-substituted 6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids as potential antimicrobial drugs
  作者：R. G. Glushkov、N. B. Marchenko、I. B. Levshin

  DOI：10.1007/bf02464104

  日期：1997.5