1,4-bis[(2-chloro-5-trifluoromethylphenyl)aminocarbonyl]-2-phenylpiperazine

• 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: 1,4-bis[(2-chloro-5-trifluoromethylphenyl)aminocarbonyl]-2-phenylpiperazine
• 英文别名: 1-N,4-N-bis[2-chloro-5-(trifluoromethyl)phenyl]-2-phenylpiperazine-1,4-dicarboxamide
• 化学式: C₂₆H₂₀Cl₂F₆N₄O₂
• 分子量: 605.367
• InChiKey: CBQXNJCWJHYYLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  40
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-苯基哌嗪 、 异氰酸- 2-氯-5-(三氟甲基)苯酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到1,4-bis[(2-chloro-5-trifluoromethylphenyl)aminocarbonyl]-2-phenylpiperazine
  参考文献：
  名称：

  Optimization of piperazine-derived ureas privileged structures for effective antiadenovirus agents

  摘要：

  In recent years, human adenovirus (HAdV) infections have shown a high clinical impact in both immunosuppressed and immunocompetent patients. The research into specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients constitutes a principal objective for medicinal chemistry due to the lack of any specific secure drug to treat these infections. In this study, we report a small-molecule library (67 compounds) designed from an optimization process of piperazinederived urea privileged structures and their biological evaluation: antiviral activity and cytotoxicity. The active compounds selected were further evaluated to gain mechanistic understanding for their inhibition. Twelve derivatives were identified that inhibited HAdV infections at nanomolar and low micromolar concentrations (IC50 from 0.6 to 5.1 mu M) with low cytotoxicity. In addition, our mechanistic assays suggested differences in the way the derivatives exert their anti-HAdV activity targeting transcription, DNA replication and later steps in the HAdV replication cycle. Furthermore, eight of the 12 studied derivatives blocked human cytomegalovirus (HCMV) DNA replication at low micromolar concentrations. The data provided herein indicates that the 12 thiourea/urea piperazine derivatives studied may represent potential lead compounds for clinical evaluation and development of new anti-HAdV drugs. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111840

文献信息

• Optimization of piperazine-derived ureas privileged structures for effective antiadenovirus agents
  作者：Sarah Mazzotta、José Antonio Marrugal-Lorenzo、Margarita Vega-Holm、Ana Serna-Gallego、Jaime Álvarez-Vidal、Judith Berastegui-Cabrera、José Pérez del Palacio、Caridad Díaz、Francesca Aiello、Jerónimo Pachón、Fernando Iglesias-Guerra、José Manuel Vega-Pérez、Javier Sánchez-Céspedes

  DOI：10.1016/j.ejmech.2019.111840

  日期：2020.1

  In recent years, human adenovirus (HAdV) infections have shown a high clinical impact in both immunosuppressed and immunocompetent patients. The research into specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients constitutes a principal objective for medicinal chemistry due to the lack of any specific secure drug to treat these infections. In this study, we report a small-molecule library (67 compounds) designed from an optimization process of piperazinederived urea privileged structures and their biological evaluation: antiviral activity and cytotoxicity. The active compounds selected were further evaluated to gain mechanistic understanding for their inhibition. Twelve derivatives were identified that inhibited HAdV infections at nanomolar and low micromolar concentrations (IC50 from 0.6 to 5.1 mu M) with low cytotoxicity. In addition, our mechanistic assays suggested differences in the way the derivatives exert their anti-HAdV activity targeting transcription, DNA replication and later steps in the HAdV replication cycle. Furthermore, eight of the 12 studied derivatives blocked human cytomegalovirus (HCMV) DNA replication at low micromolar concentrations. The data provided herein indicates that the 12 thiourea/urea piperazine derivatives studied may represent potential lead compounds for clinical evaluation and development of new anti-HAdV drugs. (C) 2019 Elsevier Masson SAS. All rights reserved.