6-(3-fluoropyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one | 881916-28-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-(3-fluoropyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one
• 英文别名: 2-(morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one；6-(3-fluoropyridin-4-yl)-3-methyl-2-morpholin-4-ylpyrimidin-4-one
• CAS: 881916-28-5
• 化学式: C₁₄H₁₅FN₄O₂
• 分子量: 290.297
• InChiKey: GKIMUJASQWOVNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(3-fluoropyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one 、 4-氟苯乙胺 反应 8.0h， 生成 6-[3-[2-(4-Fluorophenyl)ethylamino]pyridin-4-yl]-3-methyl-2-morpholin-4-ylpyrimidin-4-one
  参考文献：
  名称：

  [EN] 6- (PYRIDINYL) -4-PYRIMIDONE DERIVATES AS TAU PROTEIN KINASE 1 INHIBITORS
  [FR] COMPOSE PYRIMIDONE

  摘要：

  公开号：

  WO2006036015A3
• 作为产物：
  描述：

  3-氟吡啶 在 Carbonyldiimidazole 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.0h， 生成 6-(3-fluoropyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one
  参考文献：
  名称：

  Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer’s disease

  摘要：

  We herein describe the results of further evolution of GSK-3 beta inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3 beta inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.005

文献信息

• 6- (PYRIDINYL) -4-PYRIMIDONE DERIVATES AS TAU PROTEIN KINASE 1 INHIBITORS
  申请人：Watanabe Kazutoshi

  公开号：US20090239864A1

  公开（公告）日：2009-09-24

  A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R 1 represents a C 1 -C 12 alkyl; R 2 represents a hydrogen atom or the like; R 3 represents a halogen or the like; q represents an integer of 1 to 7; R 4 represents a halogen or the like; p represents 0 or an integer of 1 to 5; R 5 represents a C 6 -C 10 aryl, a heterocycle or the like; and X represents oxygen, NH, or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

  化合物的化学式为（I），其手性异构体，或其药学可接受的盐：其中R1表示C1-C12烷基；R2表示氢原子或类似物；R3表示卤素或类似物；q表示1至7的整数；R4表示卤素或类似物；p表示0或1至5的整数；R5表示C6-C10芳基，杂环或类似物；X表示氧，NH或类似物，用于预防和/或治疗由tau蛋白激酶1高活性引起的疾病，例如神经退行性疾病（如阿尔茨海默病）。
• 6-(pyridinyl)-4-pyrimidone derivates as tau protein kinase 1 inhibitors
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：US08129377B2

  公开（公告）日：2012-03-06

  A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R1 represents a C1-C12 alkyl; R2 represents a hydrogen atom or the like; R3 represents a halogen or the like; q represents an integer of 1 to 7; R4 represents a halogen or the like; p represents 0 or an integer of 1 to 5; R5 represents a C6-C10 aryl, a heterocycle or the like; and X represents oxygen, NH, or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

  化合物的化学式为（I），其手性异构体或药物可接受的盐：其中，R1代表C1-C12烷基；R2代表氢原子或类似物；R3代表卤素或类似物；q代表1至7的整数；R4代表卤素或类似物；p代表0或1至5的整数；R5代表C6-C10芳基，杂环或类似物；X代表氧、NH或类似物，用于预防和/或治疗由tau蛋白激酶1过度活化引起的疾病，如神经退行性疾病（例如阿尔茨海默病）。
• 6-(Pyridinyl)-4-pyrimidone derivatives as tau protein kinase 1 inhibitors
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP2261224A2

  公开（公告）日：2010-12-15

  A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R1 represents a C1-C12 alkyl; R2 represents a hydrogen atom or the like; R3 represents a halogen or the like; q represents an integer of 1 to 7; R4 represents a halogen or the like; p represents 0 or an integer of 1 to 5; R5 represents a C6-C10 aryl, a heterocycle or the like; and X represents oxygen, NH, or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

  由式（I）代表的化合物、其光学活性异构体或其药物可接受盐：其中 R1 代表 C1-C12 烷基；R2 代表氢原子或类似物；R3 代表卤素或类似物；q 代表 1 至 7 的整数；R4 代表卤素或类似物；p 代表 0 或 1 至 5 的整数；R5 代表 C6-C10 芳基、杂环或类似物；X 代表氧、NH 或类似物，用于预防和/或治疗由 tau 蛋白激酶 1 活性亢进引起的疾病，如神经退行性疾病（如阿尔茨海默病）。如阿尔茨海默病）。
• 6-(PYRIDINYL)-4-PYRIMIDONE DERIVATES AS TAU PROTEIN KINASE 1 INHIBITORS
  申请人：Mitsubishi Pharma Corporation

  公开号：EP1805164A2

  公开（公告）日：2007-07-11
• US8129377B2
  申请人：——

  公开号：US8129377B2

  公开（公告）日：2012-03-06