2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one | 402560-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
• 英文别名: 2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrimido[1,2a]pyrimidin-4-one；2-Pyridin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one；2-Pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one；2-pyridin-4-yl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one
• CAS: 402560-87-6
• 化学式: C₁₂H₁₂N₄O
• 分子量: 228.253
• InChiKey: TUQPSMBVVMPFJS-UHFFFAOYSA-N

物化性质

• 沸点：
  412.1±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one 在 nitronium tetrafluoborate 、 rubidium fluoride 、 sodium hydroxide 作用下， 以 1,2-二氯乙烷 、 水 为溶剂， 生成 3-nitro-2-pyridin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Substituted heterocyclic compounds and methods of use

  摘要：

  本发明涉及具有一般公式的化合物或其药学上可接受的盐，其中R1是饱和或不饱和的5、6或7成员环，其中含有0、1、2或3个从N、O和S中选择的原子，环可能与苯基融合，并被0、1或2个氧代基取代，而且R1还被取代；R2是取代的C1-6烷基。还包括一种用于预防或治疗炎症、类风湿关节炎、帕吉特氏病、骨质疏松症、多发性骨髓瘤、葡萄膜炎、急性或慢性骨髓性白血病、胰岛素β细胞破坏、骨关节炎、类风湿脊柱炎、痛风性关节炎、炎症性肠病、成人呼吸窘迫综合征（ARDS）、牛皮癣、克罗恩病、过敏性鼻炎、溃疡性结肠炎、过敏反应、接触性皮炎、哮喘、肌肉退化、虚弱症、雷特综合征、1型糖尿病、2型糖尿病、骨吸收性疾病、移植物抗宿主反应、阿尔茨海默病、中风、心肌梗死、缺血再灌注损伤、动脉粥样硬化、脑外伤、多发性硬化、脑疟、败血症、脓毒性休克、中毒性休克综合征、发热、HIV-1、HIV-2、HIV-3、巨细胞病毒（CMV）、流感、腺病毒、疱疹病毒或带状疱疹感染引起的肌肉疼痛的方法，该方法包括向哺乳动物施用上述化合物的有效量。

  公开号：

  US20050020592A1
• 作为产物：
  描述：

  异烟酰乙酸乙酯 、 2-氨基-1,4,5,6-四氢嘧啶盐酸盐 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以75%的产率得到2-(pyridin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  9-[Alkyl], 9-[(heteroaryl)alkyl] and 9-[(aryl)alkyl]-2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives

  摘要：

  该发明涉及一种由式(I)表示的6,7,8,9-四氢嘧啶[1,2-a]嘧啶酮衍生物或其盐：其中：X代表氢原子、硫原子或氧原子；Y代表键、双键、三键、氧原子、硫原子、磺酰基、磺氧基、羰基、氮原子，氮原子可以选择性地被C1-6烷基、苯基或苄基取代，或者一个或两个取代基取代的亚甲基基团；R1代表2,3或4-吡啶基，可以选择性地被C1-4烷基、C1-4烷氧基或卤原子取代；当Y代表键、可以选择性取代的亚甲基基团或羰基时，R2代表C1-6烷基、C1-4烷硫基、C1-4烷氧基、C3-6环烷基、萘基、苯硫基、苄基、苯环、吡啶环、吲哚环、吡咯环、噻吩环、呋喃环或咪唑环；苄基、苯基、萘基或环可以选择性地被1至3个取代基取代；当Y代表双键、三键、氧原子、硫原子、磺酰基、磺氧基或可以选择性取代的氮原子时，R2代表C1-6烷基、C3-6环烷基、萘基、苄基、苯环、吡啶环、吲哚环、吡咯环、噻吩环、呋喃环或咪唑环，苄基或苯基、萘基或环可以选择性地被1至3个取代基取代；n代表0至3。该发明还涉及一种药物，包括所述衍生物或其盐，作为用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病的活性成分。

  公开号：

  EP1184383A1

文献信息

• 9-[Alkyl], 9-[(heteroaryl)alkyl] and 9-[(aryl)alkyl]-2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives
  申请人：SANOFI-SYNTHELABO

  公开号：EP1184383A1

  公开（公告）日：2002-03-06

  The invention relates to a 6,7,8,9-tetrahydropyrimido [1,2-a] pyrimidone derivative represented by formula (I) or a salt thereof: wherein: X represents hydrogen atoms, a sulphur atom or an oxygen atom; Y represents a bond, a double bond, a triple bond, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxyde group, a carbonyl group, a nitrogen atom being optionally substituted by a C1-6 alkyl group, a phenyl or a benzyl group; or a methylene group optionally substituted by one or two substituents; R1 represents a 2, 3 or 4-pyridyl group optionally substituted by a C1-4 alkyl group, a C1-4 alkoxy group or a halogen atom; when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C1-6 alkyl group, a C1-4 alkylthio group, a C1-4 alkoxy group, a C3-6 cycloalkyl group, a naphthyl group, a phenylthio group, a benzyl group, a phenyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring ; the benzyl group, the phenyls, the naphthyl or the rings being optionally substituted by 1 to 3 substituents; when Y represents a double bond, a triple bond, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxyde group or a nitrogen atom being optionally substituted then R2 represents a C1-6 alkyl group, a C3-6 cycloalkyl group, a naphthyl group, a benzyl group, a phenyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring, the benzyl group or the phenyls, the naphthyl or the rings being optionally substituted by 1 to 3 substituents ; and n represents 0 to 3. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β.

  该发明涉及一种由式(I)表示的6,7,8,9-四氢嘧啶[1,2-a]嘧啶酮衍生物或其盐：其中：X代表氢原子、硫原子或氧原子；Y代表键、双键、三键、氧原子、硫原子、磺酰基、磺氧基、羰基、氮原子，氮原子可以选择性地被C1-6烷基、苯基或苄基取代，或者一个或两个取代基取代的亚甲基基团；R1代表2,3或4-吡啶基，可以选择性地被C1-4烷基、C1-4烷氧基或卤原子取代；当Y代表键、可以选择性取代的亚甲基基团或羰基时，R2代表C1-6烷基、C1-4烷硫基、C1-4烷氧基、C3-6环烷基、萘基、苯硫基、苄基、苯环、吡啶环、吲哚环、吡咯环、噻吩环、呋喃环或咪唑环；苄基、苯基、萘基或环可以选择性地被1至3个取代基取代；当Y代表双键、三键、氧原子、硫原子、磺酰基、磺氧基或可以选择性取代的氮原子时，R2代表C1-6烷基、C3-6环烷基、萘基、苄基、苯环、吡啶环、吲哚环、吡咯环、噻吩环、呋喃环或咪唑环，苄基或苯基、萘基或环可以选择性地被1至3个取代基取代；n代表0至3。该发明还涉及一种药物，包括所述衍生物或其盐，作为用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病的活性成分。
• 2-pyridinyl-6,7,8,9-tetrahydropyrimido{1,2-a}pyrimidin-4-one and 7-pyridinyl-1,3-dihydoimidazo{1,2-a}pyrimidin-5(1h)one derivatives
  申请人：——

  公开号：US20040087598A1

  公开（公告）日：2004-05-06

  The invention relates to pyrimidone derivative represented by formula (I) or a salt thereof wherein X represents hydrogen atoms, a sulfur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group, a 1,2-cyclopropylene, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxyde group, a carbonyl group, a nitrogen atom being optionally substituted; or a methylene group optionally substituted; R1 represent a 2,3 or 4-pyridyl group optionally substituted by a C 3-6 cycloalkyl group a C 1-4 alkyl group, a C 1-4 alkoxy group, a benzyl group or a halogen atom; when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represent a C 1-16 alkyl group, a C 3-6 cycloalkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a 5,6,7,8-tetrahydronaphthyl ring, a naphthyl ring, a phenylthio group, a benzyl group, a phenyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; when Y represents an ethenylene group, an ethynylene group, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxyde group or a nitrogen atom being optionally substituted then R2 represents a C 1-6 alkyl group, a C 3-6 cycloalkyl group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a naphthyl ring, a 5,6,7,8-tetrahydronaphthyl ring, a benzyl group, a phenyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring. And a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative diseases caused by abnormal activity of GSK3&bgr; such as Alzheimer's disease.

  本发明涉及一种以式（I）表示的嘧啶酮衍生物或其盐，其中X代表氢原子、硫原子、氧原子或C1-2烷基和氢原子；Y代表键，乙烯基，乙炔基，1,2-环丙烷基，氧原子，硫原子，磺酰基，磺酸氧化物基，羰基，氮原子（可选择性取代）或取代的亚甲基基团；R1代表2,3或4-吡啶基团，可选择性取代为C3-6环烷基，C1-4烷基，C1-4烷氧基，苄基或卤原子；当Y代表键，可选择性取代的亚甲基基团或羰基时，则R2代表C1-16烷基，C3-6环烷基，C1-4烷硫基，C1-4烷氧基，C1-2全氟烷基，C1-3卤代烷基，5,6,7,8-四氢萘基环，萘基环，苯硫基，苄基，苯基环，吡啶基环，吲哚基环，吡咯基环，噻吩基环，呋喃基环或咪唑基环；当Y代表乙烯基，乙炔基，氧原子，硫原子，磺酰基，磺酸氧化物基或可选择性取代的氮原子时，则R2代表C1-6烷基，C3-6环烷基，C1-2全氟烷基，C1-3卤代烷基，萘基环，5,6,7,8-四氢萘基环，苄基，苯基环，吡啶基环，吲哚基环，吡咯基环，噻吩基环，呋喃基环或咪唑基环。本发明还涉及一种药物，其包含所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，例如阿尔茨海默病。
• 2-Pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-A]pyrimidin-4-one and 7-pyridinyl-2,3-dihydoimidazo[1,2-A]pyrimidin-5(1H)one derivatives
  申请人：Almario Garcia Antonio

  公开号：US20060014762A1

  公开（公告）日：2006-01-19

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof: wherein: X represents hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group, a 1,2-cyclopropylene, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxyde group, a carbonyl group, a nitrogen atom being optionally substituted; or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridyl group optionally substituted by a C 3-6 cycloalkyl group a C 1-4 alkyl group, a C 1-4 alkoxy group, a benzyl group or a halogen atom; when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C 1-6 alkyl group, a C 3-6 cycloalkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a 5,6,7,8-tetrahydronaphthyl ring, a naphthyl ring, a phenylthio group, a benzyl group, a phenyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; when Y represents an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxyde group or a nitrogen atom being optionally substituted then R2 represents a C 1-6 alkyl group, a C 3-6 cycloalkyl group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a naphthyl ring, a 5,6,7,8-tetrahydronaphthyl ring, a benzyl group, a phenyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring. And a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative diseases caused by abnormal activity of GSK3β such as Alzheimer's disease.

  本发明涉及一种由式（I）或其盐所表示的嘧啶酮衍生物：其中：X代表氢原子，硫原子，氧原子或C1-2烷基和氢原子；Y代表键，乙烯基，乙炔基，1,2-环丙基，氧原子，硫原子，磺酰基，磺酸氧基，羰基，氮原子（可选地被取代）或取代的亚甲基基团；R1代表2、3或4-吡啶基团，可选地被C3-6环烷基，C1-4烷基，C1-4烷氧基，苄基或卤原子取代；当Y代表键，可选地被取代的亚甲基基团或羰基时，R2代表C1-6烷基，C3-6环烷基，C1-4烷硫基，C1-4烷氧基，C1-2全卤代烷基，C1-3卤代烷基，5,6,7,8-四氢萘基环，萘基环，苯基硫基，苄基，苯基环，吡啶基环，吲哚基环，吡咯基环，噻吩基环，呋喃基环或咪唑基环；当Y代表乙烯基，乙炔基，氧原子，硫原子，磺酰基，磺酸氧基或可选地被取代的氮原子时，R2代表C1-6烷基，C3-6环烷基，C1-2全卤代烷基，C1-3卤代烷基，萘基环，5,6,7,8-四氢萘基环，苄基，苯基环，吡啶基环，吲哚基环，吡咯基环，噻吩基环，呋喃基环或咪唑基环。本发明还涉及一种药物，其包含所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。
• HETEROARYL SUBSTITUTED 2-PYRIDINYL AND 2-PYRIMIDINYL -6,7,8,9-TETRAHYDROPYRIMIDO[1,2-a] PYRIMIDIN-4-ONE DERIVATIVES
  申请人：LOCHEAD Alistair

  公开号：US20070225300A1

  公开（公告）日：2007-09-27

  The invention relates to use of a pyrimidone derivative represented by formula (I) or a salt thereof wherein: X, Y, R1, R2, R3, R4, R5, m, n and p are as defined herein. In particular, the invention relates to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β or GSK3β and cdk5/p25, such as Alzheimer disease.

  本发明涉及使用由式（I）表示的嘧啶酮衍生物或其盐，其中：X，Y，R1，R2，R3，R4，R5，m，n和p如本文所定义。具体而言，本发明涉及一种药物，其包含所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活性引起的神经退行性疾病，如阿尔茨海默病。
• Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives
  申请人：Sanofi-Aventis

  公开号：US07232827B2

  公开（公告）日：2007-06-19

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: (I) X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring optionally substituted; R2 represents a heterocyclic bicyclic rings, having 1–4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom and having 5–9 carbon atoms, of formula (II) R3 represents a hydrogen atom, a C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom; R4 represents a hydrogen atom, a C1-6 alkyl group, a C1-4 alkoxy group or a halogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β or GSK3β and cdk5/p25, such as Alzheimer disease

  本发明涉及一种由公式（I）表示的嘧啶酮衍生物或其盐，其中：（I）X代表两个氢原子，一个硫原子，一个氧原子或C1-2烷基和一个氢原子；Y代表键，乙烯基，乙炔基或甲基烷基，可选地被取代；R1代表2，3或4-吡啶环或2，4或5-嘧啶环，可选地被取代；R2代表具有1-4个杂原子的杂环双环环，所述杂原子选择自氧原子，硫原子和氮原子，并且具有5-9个碳原子，公式为（II）R3代表氢原子，C1-6烷基，羟基，C1-4烷氧基或卤素原子；R4代表氢原子，C1-6烷基，C1-4烷氧基或卤素原子。本发明还涉及一种药物，其中包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活性引起的神经退行性疾病，例如阿尔茨海默病。