6-methyl-5-(2-methyl-1,3-thiazol-4-yl)-2-oxo-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: 6-methyl-5-(2-methyl-1,3-thiazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile
• 英文别名: 1,2-dihydro-6-methyl-5-(2-methyl-4-thiazolyl)-2-oxo-3-pyridinecarbonitrile；6-methyl-5-(2-methyl-1,3-thiazol-4-yl)-2-oxo-1H-pyridine-3-carbonitrile
• 化学式: C₁₁H₉N₃OS
• 分子量: 231.278
• InChiKey: QFMUACRQXSEPBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  94
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methyl-5-(2-methyl-1,3-thiazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile 生成 1,2-dihydro-6-methyl-5-(2-methyl-4-thiazolyl)-2-oxo-3-pyridinecarboxamide
  参考文献：
  名称：

  LESHER, G. Y.;SINGH, BALDEV

  摘要：

  DOI：
• 作为产物：
  描述：

  5-bromoacetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile 、 硫代乙酰胺 在 水 、 ammonium hydroxide 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以to produce 8.8 g of 1,2-dihydro-6-methyl-5-(2-methyl-4-thiazolyl)-2-oxo-3-pyridinecarbonitrile, m.p. 305°-307° C. with decomposition的产率得到6-methyl-5-(2-methyl-1,3-thiazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile
  参考文献：
  名称：

  5-.alpha.-bromoalkanoyl-2-oxo-3-pyridinecarbonitriles

  摘要：

  3-Q-4-R.sub.2 -5-(2-Q'-5-R.sub.3 -4-噻唑基)-6-R.sub.1 -2(1H)-吡啶酮(I)，其中R.sub.1是具有一到四个碳原子的烷基，R.sub.2是氢或甲基，R.sub.3是氢或具有一到三个碳原子的烷基，Q是氨基，氨基甲酰基，羧基，氰基或氢，Q'是具有一到四个碳原子的烷基，氨基或R.sub.4 NH，其中R.sub.4是具有一到四个碳原子的烷基，或其酸加成盐，其中至少有一个Q和Q'是氨基或Q'是R.sub.4 NH，可用作心脏强心剂（当Q为氨基，氰基或氢时的I）和/或中间体（当Q为氰基，氨基甲酰基或羧基时的I）。还显示了1,2-二氢-4-R.sub.2 -5-[R.sub.3 CH(Br)CO]-6-R.sub.1 -2-氧代-3-吡啶基腈（II）作为中间体，并且还提供了制备I和II的方法。

  公开号：

  US04595762A1

文献信息

• 5-(4-Thiazolyl)-6-alkyl-2(1H)-pyridinones and their cardiotonic use
  申请人：Sterling Drug Inc.

  公开号：US04469699A1

  公开（公告）日：1984-09-04

  3-Q-4-R.sub.2 -5-(2-Q'-5-R.sub.3 -4-thiazolyl)-6-R.sub.1 -2(1H)-pyridinones (I), where R.sub.1 is alkyl having from one to four carbon atoms, R.sub.2 is hydrogen or methyl, R.sub.3 is hydrogen or alkyl having from one to three carbon atoms, Q is amino, carbamyl, carboxy, cyano or hydrogen, and Q' is alkyl having from one to four carbon atoms, amino or R.sub.4 NH where R.sub.4 is alkyl having from one to four carbon atoms, or acid-addition salts thereof where at least one of Q and Q' is amino or Q' is R.sub.4 NH, are useful as cardiotonics (I where Q is amino, cyano or hydrogen) and/or as intermediates (I where Q is cyano, carbamyl or carboxy). Also shown as intermediates are 1,2-dihydro-4-R.sub.2 -5-[R.sub.3 CH(Br)CO]-6-R.sub.1 -2-oxo-3-pyridinecarbonitriles (II), and, also, processes for preparing I and II.

  3-Q-4-R.sub.2 -5-(2-Q'-5-R.sub.3 -4-噻唑基)-6-R.sub.1 -2(1H)-吡啶酮(I)，其中R.sub.1是具有一至四个碳原子的烷基，R.sub.2是氢或甲基，R.sub.3是氢或具有一至三个碳原子的烷基，Q是氨基，氨基甲酰基，羧基，氰基或氢，而Q'是具有一至四个碳原子的烷基，氨基或R.sub.4 NH，其中R.sub.4是具有一至四个碳原子的烷基，或它们的酸加成盐，其中至少有一个Q和Q'为氨基或Q'为R.sub.4 NH，可用作心脏强心剂（其中Q为氨基，氰基或氢）和/或中间体（其中Q为氰基，氨基甲酰基或羧基）。还显示了1,2-二氢-4-R.sub.2 -5-[R.sub.3 CH(Br)CO]-6-R.sub.1 -2-氧代-3-吡啶基腈(II)作为中间体，以及制备I和II的方法。
• 5-(2-Substituted-4-thiazolyl)-6-alkyl-2(1H)-pyridinones and cardiotonic
  申请人：Sterling Drug Inc.

  公开号：US04539327A1

  公开（公告）日：1985-09-03

  3-Q-4-R.sub.2 -5-(2-Q'-5-R.sub.3 -4-thiazolyl)-6-R.sub.1 -2(1H)-pyridinones (I), where R.sub.1 is alkyl having from one to four carbon atoms, R.sub.2 is hydrogen or methyl, R.sub.3 is hydrogen or alkyl having from one to three carbon atoms, Q is amino, carbamyl, carboxy, cyano or hydrogen, and Q' is alkyl having from one to four carbon atoms, amino or R.sub.4 NH where R.sub.4 is alkyl having from one to four carbon atoms, or acid-addition salts thereof where at least one of Q and Q' is amino or Q' is R.sub.4 NH, are useful as cardiotonics (I where Q is amino, cyano or hydrogen) and/or as intermediates (I where Q is cyano, carbamyl or carboxy). Also shown as intermediates are 1,2-dihydro-4-R.sub.2 -5-[R.sub.3 CH(Br)CO]-6-R.sub.1 -2-oxo-3-pyridinecarbonitriles (II), and, also, processes for preparing I and II.

  3-Q-4-R.sub.2 -5-(2-Q'-5-R.sub.3 -4-噻唑基)-6-R.sub.1 -2(1H)-吡啶酮(I)，其中R.sub.1是具有一到四个碳原子的烷基，R.sub.2是氢或甲基，R.sub.3是氢或具有一到三个碳原子的烷基，Q是氨基，氨基甲酰基，羧基，氰基或氢，而Q'是具有一到四个碳原子的烷基，氨基或R.sub.4 NH，其中R.sub.4是具有一到四个碳原子的烷基，或其酸加成盐，其中至少一个Q和Q'是氨基或Q'是R.sub.4 NH，可用作心力衰竭药物(I，其中Q为氨基，氰基或氢)，和/或中间体(I，其中Q为氰基，氨基甲酰基或羧基)。还显示了1,2-二氢-4-R.sub.2 -5-[R.sub.3 CH(Br)CO]-6-R.sub.1 -2-氧代-3-吡啶碳腈(II)作为中间体，以及制备I和II的过程。
• 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 J. Michael

  公开号：US20070037855A1

  公开（公告）日：2007-02-15

  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.

  提供的化合物可用于治疗与阿尔茨海默淀粉样蛋白在大脑中积累有关的疾病，例如阿尔茨海默病。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进入，其中细胞可以选择性地过度表达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的异常高磷酸化）和与阿尔茨海默淀粉样蛋白在大脑中积累有关的微胶质细胞增生的方法。此外，还提供了通过给动物或人类施用诊断有效量的抑制电容性钙离子进入细胞的化合物来诊断与阿尔茨海默淀粉样蛋白在大脑中积累有关的疾病的方法。
• 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。