4-(3-nitrophenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(3-nitrophenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile
• 英文别名: 6-(4-methylphenyl)-4-(3-nitrophenyl)-2-oxo-1H-pyridine-3-carbonitrile
• 化学式: C₁₉H₁₃N₃O₃
• 分子量: 331.331
• InChiKey: OUEHPPYWIBSWRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  间硝基苯甲醛 、 氰乙酸乙酯 、 对甲基苯乙酮 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 以81 %的产率得到4-(3-nitrophenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile
  参考文献：
  名称：

  合成吡啶酮作为 α-淀粉酶和 α-葡萄糖苷酶双重抑制剂和潜在抗氧化剂的生物评价

  摘要：

  在此，设计、合成了一个新型吡啶酮衍生物1-34库，并评估了 α-淀粉酶和 α-葡萄糖苷酶抑制以及抗氧化活性。吡啶酮衍生物1-34通过各种取代的芳香醛、苯乙酮、氰基乙酸乙酯和乙酸铵在无水乙醇中的一锅多组分反应合成。通过不同的光谱技术对合成化合物1-34进行了结构表征。大多数测试化合物显示出比标准阿卡波糖（IC 50  = 14.87 ± 0.16 µM）更有希望的抑制潜力，但发现化合物13和12是最有效的化合物，IC 50针对α-淀粉酶和α-葡萄糖苷酶的值分别为 9.20 ± 0.14 µM 和 3.05 ± 0.18 µM。 在 DPPH 自由基清除活性 中，与对照丁基化羟基甲苯 (BHT)（IC 50 = 66.50 ± 0.36 µM）相比，化合物1–34在 IC 50 = 96.50 ± 0.45 至 189.98 ± 1.00 µM范围内也显示出适度的抗氧化潜力。此外，所有合成衍生

  DOI：

  10.1002/ardp.202200400

文献信息

• Compounds for inhibiting beta-amyloid production and methods of identifying the compounds
  申请人：Mullan J. Michael

  公开号：US20060188938A1

  公开（公告）日：2006-08-24

  Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods for screening for such compounds, by measuring capacitative calcium entry in cells which optionally overexpress APP or a fragment thereof. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of compounds which inhibit capacitative calcium entry in cells.

  提供了对治疗与阿尔茨海默病相关的脑部淀粉样蛋白沉积疾病（如阿尔茨海默病）有用的化合物。还提供了筛选此类化合物的方法，通过测量细胞中的电容性钙离子入流，该细胞可选择过表达APP或其片段。还提供了通过给予治疗有效量的化合物来治疗或降低β-淀粉样蛋白产生、β-淀粉样蛋白沉积、β-淀粉样蛋白神经毒性（包括tau异常的超磷酸化）和与阿尔茨海默病相关的微胶质细胞病的风险的方法，这些化合物降低细胞中的β-淀粉样蛋白产生和电容性钙离子入流。此外，还提供了通过给予诊断有效量的化合物来诊断动物或人类中与阿尔茨海默病相关的脑部淀粉样蛋白沉积疾病的方法，这些化合物抑制细胞中的电容性钙离子入流。
• Compounds and Combinations Thereof for Inhibiting Beta-Amyloid Production and Methods of Use Thereof
  申请人：Paris Daniel

  公开号：US20080058330A1

  公开（公告）日：2008-03-06

  Provided are compounds which can be used in combination for treating diseases associated with a condition associated with cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which in combination can decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of the compounds.

  提供了一些化合物，可以组合使用来治疗与阿尔茨海默病淀粉样蛋白相关的疾病，如阿尔茨海默病。还提供了一种方法，通过给予治疗有效量的化合物组合来减少β-淀粉样蛋白的产生和细胞中的电容性钙离子进入，从而治疗或降低发生β-淀粉样蛋白产生、β-淀粉样蛋白沉积、β-淀粉样蛋白神经毒性（包括tau异常过度磷酸化）和与阿尔茨海默病淀粉样蛋白相关的微胶质病变。此外，还提供了一种方法，通过给予诊断有效量的化合物来诊断动物或人类中与阿尔茨海默病淀粉样蛋白相关的疾病。
• Compounds for Inhibiting Beta-Amyloid Production and Methods of Identifying the Compounds
  申请人：Mullan Michael J.

  公开号：US20100215735A1

  公开（公告）日：2010-08-26

  Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods for screening for such compounds, by measuring capacitative calcium entry in cells which optionally overexpress APP or a fragment thereof. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of compounds which inhibit capacitative calcium entry in cells.

  提供了一些化合物，可用于治疗与阿尔茨海默氏淀粉样物质在大脑中积累有关的疾病，如阿尔茨海默病。还提供了筛选这些化合物的方法，通过测量在细胞中的电容性钙离子进入，这些细胞可以选择性地过表达APP或其片段。还提供了通过给予治疗有效量的化合物来治疗或降低发生β-淀粉样物质产生、β-淀粉样物质沉积、β-淀粉样物质神经毒性（包括tau异常过磷酸化）和与阿尔茨海默氏淀粉样物质在大脑中积累有关的小胶质细胞增生的风险的方法，这些化合物可以减少β-淀粉样物质产生和细胞中的电容性钙离子进入。此外，还提供了通过给动物或人体内给予诊断有效量的化合物来诊断与阿尔茨海默氏淀粉样物质在大脑中积累有关的疾病的方法，这些化合物可以抑制细胞中的电容性钙离子进入。
• Regioselective syntheses of 2-oxopyridine carbonitrile derivatives and evaluation for antihyperglycemic and antioxidant potential
  作者：Faiza Saleem、Maham Haider、Khalid Mohammed Khan、Musa Özil、Nimet Baltaş、Zaheer Ul-Haq、Urooj Qureshi、Uzma Salar、Muhammad Taha、Shehryar Hameed、Nisar Ullah

  DOI：10.1016/j.ijbiomac.2023.124589

  日期：2023.6

  and all thirty-four (34) compounds were found to be new. All synthetic compounds were examined for antidiabetic and antioxidant potential. The compounds exhibited α-glucosidase inhibitory potential in the range of IC50 = 3.00 ± 0.11–43.35 ± 0.67 μM and α-amylase inhibition potential in the range of IC50 = 9.20 ± 0.14–65.56 ± 1.05 μM. Among the tested compounds, 1 showed the most significant α-glucosidase

  通过区域选择性亲核取代反应合成了2-氧代吡啶腈1-34库。在第一步中，一锅多组分反应产生吡啶酮中间体。然后将生成的吡啶酮中间体与苯甲酰卤在 DMF 中反应，并在 100 °C 下搅拌 1 小时，以良好的产率提供所需的化合物。合成分子的结构通过 EI-MS、HREI-MS、1 H NMR 和13 C NMR 进行表征，发现所有三十四 (34) 种化合物都是新的。检查了所有合成化合物的抗糖尿病和抗氧化潜力。这些化合物在IC 50  = 3.00 ± 0.11–43.35 ± 0.67 μM 和IC 50 = 9.20 ± 0.14–65.56 ± 1.05 μM范围内的α-淀粉酶抑制潜力 。在所测试的化合物中，1显示出最显着的α-葡萄糖苷酶抑制活性，IC 50值为 3.00 ± 0.11 μM，而对α-淀粉酶活性最强的化合物是6，IC 50值为 9.20 ± 0.14 μM。动力学研究和分析表
• Bioevaluation of synthetic pyridones as dual inhibitors of α‐amylase and α‐glucosidase enzymes and potential antioxidants
  作者：Faiza Saleem、Khalid Mohammed Khan、Nisar Ullah、Musa Özil、Nimet Baltaş、Shehryar Hameed、Uzma Salar、Abdul Wadood、Ashfaq Ur Rehman、Mukesh Kumar、Muhammad Taha、Syed Moazzam Haider

  DOI：10.1002/ardp.202200400

  日期：2023.1

  Herein, a library of novel pyridone derivatives 1–34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1–34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1–34 were

  在此，设计、合成了一个新型吡啶酮衍生物1-34库，并评估了 α-淀粉酶和 α-葡萄糖苷酶抑制以及抗氧化活性。吡啶酮衍生物1-34通过各种取代的芳香醛、苯乙酮、氰基乙酸乙酯和乙酸铵在无水乙醇中的一锅多组分反应合成。通过不同的光谱技术对合成化合物1-34进行了结构表征。大多数测试化合物显示出比标准阿卡波糖（IC 50  = 14.87 ± 0.16 µM）更有希望的抑制潜力，但发现化合物13和12是最有效的化合物，IC 50针对α-淀粉酶和α-葡萄糖苷酶的值分别为 9.20 ± 0.14 µM 和 3.05 ± 0.18 µM。 在 DPPH 自由基清除活性 中，与对照丁基化羟基甲苯 (BHT)（IC 50 = 66.50 ± 0.36 µM）相比，化合物1–34在 IC 50 = 96.50 ± 0.45 至 189.98 ± 1.00 µM范围内也显示出适度的抗氧化潜力。此外，所有合成衍生