1-(benzofuran-2-carbonyl)-3-methylpiperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 1-(benzofuran-2-carbonyl)-3-methylpiperazine
• 英文别名: 1-Benzofuran-2-yl-(3-methylpiperazin-1-yl)methanone
• 化学式: C₁₄H₁₆N₂O₂
• mdl: MFCD21007272
• 分子量: 244.293
• InChiKey: LQTLUZLNGDQSHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(benzofuran-2-carbonyl)-3-methylpiperazine 、 异氰酸对硝基苯 以 二氯甲烷 为溶剂， 以59%的产率得到4-(benzofuran-2-carbonyl)-2-methyl-1-[(4-nitrophenyl)-aminocarbonyl]piperazine
  参考文献：
  名称：

  新的4-酰基-1-苯基氨基羰基-2-苯基哌嗪衍生物可作为腺病毒感染的潜在抑制剂。合成，生物学评估和构效关系

  摘要：

  寻找用于治疗免疫受损患者中的HAdV感染的人类腺病毒（HAdV）特异性抗病毒药物仍然是药物化学研究的一个挑战性目标。在这里，我们报告了一个小分子文库的合成，生物学评估以及结构-活性关系。我们已经确定了六种显着抑制HAdV感染的苯基哌嗪衍生物。这六个化合物显示出在低微摩尔浓度下具有阻断HAdV和人巨细胞病毒（HCMV）复制的能力，几乎没有或没有细胞毒性。根据我们的生物学研究，这些分子在生命周期的不同阶段阻断了HAdV和HCMV感染，为开发新的抗病毒药物家族提供了潜在的候选药物，以治疗DNA病毒感染。

  DOI：

  10.1021/acs.jmedchem.6b00300
• 作为产物：
  描述：

  2-甲基哌嗪 、 alkaline earth salt of/the/ methylsulfuric acid 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以74%的产率得到1-(benzofuran-2-carbonyl)-3-methylpiperazine
  参考文献：
  名称：

  新的4-酰基-1-苯基氨基羰基-2-苯基哌嗪衍生物可作为腺病毒感染的潜在抑制剂。合成，生物学评估和构效关系

  摘要：

  寻找用于治疗免疫受损患者中的HAdV感染的人类腺病毒（HAdV）特异性抗病毒药物仍然是药物化学研究的一个挑战性目标。在这里，我们报告了一个小分子文库的合成，生物学评估以及结构-活性关系。我们已经确定了六种显着抑制HAdV感染的苯基哌嗪衍生物。这六个化合物显示出在低微摩尔浓度下具有阻断HAdV和人巨细胞病毒（HCMV）复制的能力，几乎没有或没有细胞毒性。根据我们的生物学研究，这些分子在生命周期的不同阶段阻断了HAdV和HCMV感染，为开发新的抗病毒药物家族提供了潜在的候选药物，以治疗DNA病毒感染。

  DOI：

  10.1021/acs.jmedchem.6b00300

文献信息

• [EN] PIPERAZINE DERIVATIVES AS ANTIVIRAL AGENTS WITH INCREASED THERAPEUTIC ACTIVITY<br/>[FR] DÉRIVÉS DE PIPÉRAZINE COMME AGENTS ANTIVIRAUX PRÉSENTANT UNE ACTIVITÉ THÉRAPEUTIQUE ACCRUE
  申请人：SERVICIO ANDALUZ DE SALUD

  公开号：WO2017144624A1

  公开（公告）日：2017-08-31

  The present invention provides 2-phenylpiperazine derivatives having a benzofuran-2-yl group which contributes to increase the antiviral activity as well as, for some substituents, the CC50, giving more active and less cytotoxic compounds. Although further optimization and characterization of their mechanisms of action will be required for these compounds, they represent strong hit candidates for the development of a new class of antiviral compounds.

  本发明提供了具有苯并呋喃-2-基团的2-苯基哌嗪衍生物，该基团有助于增加抗病毒活性，同时对于某些取代基，还增加了CC50值，从而提供了更活性更低细胞毒性的化合物。尽管这些化合物需要进一步优化和表征其作用机制，但它们代表了用于开发新型抗病毒化合物的强有力候选物。
• Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells
  作者：Emilio Guillén-Mancina、María del Rosario García-Lozano、Estefanía Burgos-Morón、Sarah Mazzotta、Pablo Martínez-Aguado、José Manuel Calderón-Montaño、José Manuel Vega-Pérez、Miguel López-Lázaro、Fernando Iglesias-Guerra、Margarita Vega-Holm

  DOI：10.3390/ijms242317041

  日期：——

  Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

  乳腺癌是女性最常见的癌症类型。虽然目前的治疗方法可以提高患者的生存率，但当病情发展到晚期（转移）时，这些治疗方法很少能治愈患者。因此，迫切需要开发出对癌细胞具有高度选择性的新型细胞毒性药物。近年来，将已获批准的药物重新用于癌症治疗已成为一种成功的策略，因此在本研究中，我们筛选了一个抗病毒哌嗪衍生化合物库作为抗癌药物。这些化合物包括一个哌嗪环和芳基脲功能，它们是几种抗乳腺癌药物中存在的特殊结构。研究测定了一组 34 个 4-酰基-2-取代的哌嗪脲衍生物对 MCF7 乳腺癌细胞和 MCF 10A 正常乳腺细胞的选择性细胞毒性活性。化合物 31、32、35 和 37 对乳腺癌细胞表现出高度的选择性抗癌活性，同时还对另一种常见的癌症--非小细胞肺癌（A549 肺癌细胞与 MRC-5 肺正常细胞）进行了测试。化合物 35 和 37 也显示出对肺癌细胞的选择性。这些结果表明，化合物 35 和 37 有可能成为开发新抗癌剂的热门化合物。
• PIPERAZINE DERIVATIVES AS ANTIVIRAL AGENTS WITH INCREASED THERAPEUTIC ACTIVITY
  申请人：Servicio Andaluz de Salud

  公开号：EP3419626A1

  公开（公告）日：2019-01-02
• 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.
• New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure–activity Relationships
  作者：Javier Sánchez-Céspedes、Pablo Martínez-Aguado、Margarita Vega-Holm、Ana Serna-Gallego、José Ignacio Candela、José Antonio Marrugal-Lorenzo、Jerónimo Pachón、Fernando Iglesias-Guerra、José Manuel Vega-Pérez

  DOI：10.1021/acs.jmedchem.6b00300

  日期：2016.6.9

  HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure–activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus

  寻找用于治疗免疫受损患者中的HAdV感染的人类腺病毒（HAdV）特异性抗病毒药物仍然是药物化学研究的一个挑战性目标。在这里，我们报告了一个小分子文库的合成，生物学评估以及结构-活性关系。我们已经确定了六种显着抑制HAdV感染的苯基哌嗪衍生物。这六个化合物显示出在低微摩尔浓度下具有阻断HAdV和人巨细胞病毒（HCMV）复制的能力，几乎没有或没有细胞毒性。根据我们的生物学研究，这些分子在生命周期的不同阶段阻断了HAdV和HCMV感染，为开发新的抗病毒药物家族提供了潜在的候选药物，以治疗DNA病毒感染。