N-(coumarin-3-yl)thiophene-2-carboxamide | 309945-70-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: N-(coumarin-3-yl)thiophene-2-carboxamide
• 英文别名: N-(coumarin-3-yl)thiophene-2-carboxamide (7)；N-(2-oxochromen-3-yl)thiophene-2-carboxamide
• CAS: 309945-70-8
• 化学式: C₁₄H₉NO₃S
• 分子量: 271.296
• InChiKey: FTTNTECCHYPEOG-UHFFFAOYSA-N

物化性质

• 沸点：
  558.1±50.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-噻吩甲酰氯 、 3-氨基香豆素 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 N-(coumarin-3-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  3-氨基香豆素是潜在的抗神经退行性疾病的多功能药物

  摘要：

  单胺氧化酶（MAO）产生活性氧（ROS），导致神经元细胞死亡，导致神经退行性变。能够同时抑制MAO和清除自由基的药物代表了有前途的多功能神经保护剂，可用于延迟或减缓神经退行性疾病的发展。在这项工作中，描述了各种取代的3-氨基豆香豆素，它们在体外对大鼠皮层神经元中的过氧化氢具有神经保护作用，并且在1,1-二苯基-2-picylhydrazyl（DPPH⋅）自由基清除试验中具有抗氧化活性。确定了MAO-B同工型的选择性和可逆抑制剂。有趣的是，对于3-苯甲酰胺基香豆素，在4位被羟基取代会消除MAO-B活性，但这些化合物在神经保护模型中仍然具有活性。对3-杂芳基酰胺衍生物的进一步评估表明，杂环的性质决定了神经保护作用。在平行人工膜通透性试验（PAMPA）中进行的评估强调了进一步改善此类化合物的血脑屏障通透性的需要。然而，本文所述的化合物遵守Libinski的5法则，表明该新型支架具有潜在的候选药物

  DOI：

  10.1002/cmdc.201500408

文献信息

• 3-Amidocoumarins as Potential Multifunctional Agents against Neurodegenerative Diseases
  作者：Maria João Matos、Fernanda Rodríguez-Enríquez、Fernanda Borges、Lourdes Santana、Eugenio Uriarte、Martín Estrada、María Isabel Rodríguez-Franco、Reyes Laguna、Dolores Viña

  DOI：10.1002/cmdc.201500408

  日期：2015.12

  cell death, causing neurodegeneration. Agents that are able to concurrently inhibit MAO and scavenge free radicals represent promising multifunctional neuroprotective agents that could be used to delay or slow the progression of neurodegenerative diseases. In this work, variously substituted 3‐amidocoumarins are described that exert neuroprotection in vitro against hydrogen peroxide in rat cortical neurons

  单胺氧化酶（MAO）产生活性氧（ROS），导致神经元细胞死亡，导致神经退行性变。能够同时抑制MAO和清除自由基的药物代表了有前途的多功能神经保护剂，可用于延迟或减缓神经退行性疾病的发展。在这项工作中，描述了各种取代的3-氨基豆香豆素，它们在体外对大鼠皮层神经元中的过氧化氢具有神经保护作用，并且在1,1-二苯基-2-picylhydrazyl（DPPH⋅）自由基清除试验中具有抗氧化活性。确定了MAO-B同工型的选择性和可逆抑制剂。有趣的是，对于3-苯甲酰胺基香豆素，在4位被羟基取代会消除MAO-B活性，但这些化合物在神经保护模型中仍然具有活性。对3-杂芳基酰胺衍生物的进一步评估表明，杂环的性质决定了神经保护作用。在平行人工膜通透性试验（PAMPA）中进行的评估强调了进一步改善此类化合物的血脑屏障通透性的需要。然而，本文所述的化合物遵守Libinski的5法则，表明该新型支架具有潜在的候选药物
• Development of novel adenosine receptor ligands based on the 3-amidocoumarin scaffold
  作者：Maria J. Matos、Santiago Vilar、Sonja Kachler、Maria Celeiro、Saleta Vazquez-Rodriguez、Lourdes Santana、Eugenio Uriarte、George Hripcsak、Fernanda Borges、Karl-Norbert Klotz

  DOI：10.1016/j.bioorg.2015.05.008

  日期：2015.8

  With the aim of finding new adenosine receptor (AR) ligands presenting the 3-amidocoumarin scaffold, a study focusing on the discovery of new chemical entities was carried out. The synthesized compounds 1-8 were evaluated in radioligand binding (A(1), A(2A) and A(3)) and adenylyl cyclase activity (A(2B)) assays in order to determine their affinity for human AR subtypes. The 3-benzamide derivative 4 showed the highest affinity of the whole series and was more than 30-fold selective for the A(3) AR (K-i = 3.24 mu M). The current study supported that small structural changes in this scaffold allowed modulating the affinity resulting in novel promising classes of A(1), A(2A), and/or A(3) AR ligands. We also performed docking calculations in hA(2A) and hA(3) to identify the hypothetical binding mode for the most active compounds. In addition, some ADME properties were calculated in order to better understand the potential of these compounds as drug candidates. (C) 2015 Elsevier Inc. All rights reserved.
• Non-Peptidic Inhibitors of AKAP/PKA Interaction
  申请人：Klussmann Enno

  公开号：US20090176773A1

  公开（公告）日：2009-07-09

  The invention relates to non-peptidic molecules which modulate, especially inhibit, the interaction of protein kinase A (PKA) and A kinase anchor proteins (AKAP) and to a host or target organism that comprises said non-peptidic compounds or recognition molecules directed to said compounds, such as e.g. antibodies or chelating agents. The invention also relates to a pharmaceutical agent, especially for use in the treatment of diseases that are associated with a disturbance of the cAMP signal path, especially insipid diabetes, hypertonia, pancreatic diabetes, duodenal ulcer, asthma, heart failure, obesity, AIDS, edema, hepatic cirrhosis, schizophrenia and others. The invention also relates to the use of the inventive molecules.
• Evaluation of Trypanocidal and Antioxidant Activities of a Selected Series of 3-amidocoumarins
  作者：Mauricio Moncada-Basualto、Michel Lapier、Juan Diego Maya、Betty Matsuhiro、Claudio Olea-Azar、Giovanna L. Delogu、Eugenio Uriarte、Lourdes Santana、Maria Joao Matose

  DOI：10.2174/1573406414666180419113437

  日期：2018.7.12

  Background: Neglected diseases are becoming more prevalent due to globalization. This has inspired active research in the development of new drugs for the treatment of parasitic diseases such as Chagas disease. Objectives: With the aim of finding new trypanocidal agents, we report the in vitro evaluation of a new series of 3-amidocoumarins with or without hydroxyl substituents at position 4 of the coumarin ring. Methods: Electrochemical and biological assays were performed in order to assess the antioxidant and trypanocidal potential of these compounds and to better understand the mechanisms involved in their activity. Results: Most of the studied compounds showed high trypanocidal activity against both epimastigote and trypomastigote forms, with IC50 values in the low micromolar range. Some of them have greater activity and selectivity than the reference compound, nifurtimox. Conclusion: Compound 2 is the most active of this series, being also non-cytotoxic against murine RAW 264.7 macrophages. Electrochemical and radical scavenging experiments were carried out, providing new information about the profile of the best derivatives, and the potential therapeutic application of the new 3-amidocoumarins.

  背景：由于全球化，被忽视的疾病变得越来越普遍。这激发了针对恰加斯病等寄生虫病治疗新药开发的活跃研究。 目的：为了寻找新的杀锥虫剂，我们报告了一系列新型3-酰胺香豆素（有无羟基取代基在香豆素环的4位）的体外评估。 方法：进行了电化学和生物学测试，以评估这些化合物的抗氧化和杀锥虫潜力，并更好地理解其活性涉及的机制。 结果：大多数研究化合物对epimastigote和trypomastigote形式都显示出高度的杀锥虫活性，IC50值在低微摩尔范围内。其中一些化合物比参考化合物硝呋莫司具有更高的活性和选择性。 结论：化合物2是该系列中最活跃的，对小鼠RAW 264.7巨噬细胞也没有细胞毒性。进行了电化学和自由基清除实验，为最佳衍生物的特性提供了新的信息，并展示了新型3-酰胺香豆素的潜在治疗应用。