ethyl 6-amino-1-methyl-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate | 304897-79-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 6-amino-1-methyl-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate
• 英文别名: Ethyl 6-amino-1-methyl-4-oxo-7-[4-(2-pyridyl)piperazin-1-yl]quinoline-3-carboxylate；ethyl 6-amino-1-methyl-4-oxo-7-(4-pyridin-2-ylpiperazin-1-yl)quinoline-3-carboxylate
• CAS: 304897-79-8
• 化学式: C₂₂H₂₅N₅O₃
• 分子量: 407.472
• InChiKey: VREZPJZIWGZIEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  92
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 6-amino-1-methyl-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以47%的产率得到6-amino-1-methyl-7-[4-(2-pyridyl)-1-piperazinyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid dihydrochloride
  参考文献：
  名称：

  6-Aminoquinolones as New Potential Anti-HIV Agents

  摘要：

  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.

  DOI：

  10.1021/jm9903390
• 作为产物：
  描述：

  ethyl 7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 镍 氢气 作用下， 以 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、207.73 kPa 条件下， 反应 6.0h， 生成 ethyl 6-amino-1-methyl-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate
  参考文献：
  名称：

  6-Aminoquinolones as New Potential Anti-HIV Agents

  摘要：

  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.

  DOI：

  10.1021/jm9903390

文献信息

• Structure−Activity Relationship Study on Anti-HIV 6-Desfluoroquinolones
  作者：Oriana Tabarrini、Serena Massari、Dirk Daelemans、Miguel Stevens、Giuseppe Manfroni、Stefano Sabatini、Jan Balzarini、Violetta Cecchetti、Christophe Pannecouque、Arnaldo Fravolini

  DOI：10.1021/jm701585h

  日期：2008.9.11

  recent findings that 6-aminoquinolones inhibit the HIV Tat-mediated transactivation, we have designed a broad series of derivatives identifying novel potent agents such as the 6-desfluoroquinolones 24 (HM12) and 27 (HM13), which showed pronounced anti-HIV activity in acutely, chronically, and latently HIV-1 infected cell cultures. We demonstrate here that highly potent molecules can be obtained by optimizing

  根据我们最近的发现，即6-氨基喹诺酮类药物抑制HIV Tat介导的反式激活，我们设计了一系列衍生物，这些衍生物可识别新型强效药物，例如6-去氟喹诺酮类药物24（HM12）和27（HM13），其表现出明显的在急性，慢性和潜在感染HIV-1的细胞培养物中具有抗HIV活性。我们在这里证明，通过优化喹诺酮核的各个位置上的取代基，可以获得高效能的分子。
• Design, Synthesis, and Evaluation of WC5 Analogues as Inhibitors of Human Cytomegalovirus Immediate-Early 2 Protein, a Promising Target for Anti-HCMV Treatment
  作者：Serena Massari、Beatrice Mercorelli、Luca Sancineto、Stefano Sabatini、Violetta Cecchetti、Giorgio Gribaudo、Giorgio Palù、Christophe Pannecouque、Arianna Loregian、Oriana Tabarrini

  DOI：10.1002/cmdc.201300106

  日期：2013.8

  of viral DNA polymerase. Therefore, compounds that target other essential viral events could overcome this problem. One example of this is the 6‐aminoquinolone WC5, which acts by directly blocking the transactivation of essential viral Early genes by the Immediate‐Early 2 (IE2) protein. In this study, the quinolone scaffold of the lead compound WC5 was investigated in depth, defining more suitable substituents

  尽管人类巨细胞病毒（HCMV）感染对具有免疫能力的个体而言大部分是无症状的，但对于那些与各种临床表现相关的免疫功能低下的人来说，它仍然是一个严重的威胁。几种可用的抗HCMV药物的治疗效用受到一些缺点的限制，包括由于其共同的作用机制（如抑制病毒DNA聚合酶）而产生的交叉耐药性。因此，靶向其他基本病毒事件的化合物可以克服这个问题。其中的一个例子是6-氨基喹诺酮WC5，它通过直接抑制Instant -Early 2（IE2）蛋白直接阻断必需的病毒Early基因的反式激活而起作用。在这项研究中，铅化合物WC5的喹诺酮骨架进行了深入研究，为所探索的每个支架位置定义了更合适的取代基，并鉴定了新颖，有效和无毒的化合物。一些化合物通过干扰依赖IE2的病毒E基因表达而显示出有效的抗HCMV活性。其中，萘啶酮1在潜伏感染的细胞中也具有强大的抗HIV活性。它们的抗病毒谱以及创新的作用机制使这些抗HCMV喹诺酮类
• 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.