1-[(4-cyanophenyl)aminothiocarbonyl]-4-(2-cyclohexylacetyl)-2-methylpiperazine

• 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: 1-[(4-cyanophenyl)aminothiocarbonyl]-4-(2-cyclohexylacetyl)-2-methylpiperazine
• 英文别名: N-(4-cyanophenyl)-4-(2-cyclohexylacetyl)-2-methylpiperazine-1-carbothioamide
• 化学式: C₂₁H₂₈N₄OS
• 分子量: 384.546
• InChiKey: OLFZIDRDIJMVEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  91.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基哌嗪 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 1-[(4-cyanophenyl)aminothiocarbonyl]-4-(2-cyclohexylacetyl)-2-methylpiperazine
  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

• Exploration of piperazine-derived thioureas as antibacterial and anti-inflammatory agents. In vitro evaluation against clinical isolates of colistin-resistant Acinetobacter baumannii
  作者：Sarah Mazzotta、Tania Cebrero-Cangueiro、Luca Frattaruolo、Margarita Vega-Holm、Marta Carretero-Ledesma、Javier Sánchez-Céspedes、Anna Rita Cappello、Francesca Aiello、Jerónimo Pachón、José Manuel Vega-Pérez、Fernando Iglesias-Guerra、María Eugenia Pachón-Ibáñez

  DOI：10.1016/j.bmcl.2020.127411

  日期：2020.9

  6.25 μM). A common structural feature in most active compounds was the presence of a 3,5-bis-trifluoromethyl phenyl ring at the thiourea function. In addition, the ability of the compounds to inhibit production of nitric oxide (NO) was examined in RAW 264.7 murine macrophages, highlighting the potential of piperazine-derived thioureas as promising scaffolds for the design of new combined anti-bact

  鲍曼不动杆菌是医院单位中最重要的耐多药微生物之一。它对多种抗生素具有抗性，因此有必要开发新的治疗策略。这项研究的目的是评估一组哌嗪衍生的硫脲对13种对大肠菌素耐药的鲍曼不动杆菌的临床菌株的抗菌活性。鉴定出六种衍生物可抑制鲍曼不动杆菌46％的细菌生长低摩尔浓度（最小抑制浓度从1.56至6.25μM）的菌株。大多数活性化合物的常见结构特征是在硫脲官能团处存在3,5-双三氟甲基苯环。此外，在RAW 264.7鼠巨噬细胞中检测了该化合物抑制一氧化氮（NO）产生的能力，突出了哌嗪衍生的硫脲作为设计新型抗菌/消炎药组合的有希望的支架的潜力。
• 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.