(1S)-1-methyl-2-(5-pyridin-3-yl-2,5-diazabicyclo[2.2.1]hept-2-yl)-1H-[4,4']bipyrimidinyl-6-one hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (1S)-1-methyl-2-(5-pyridin-3-yl-2,5-diazabicyclo[2.2.1]hept-2-yl)-1H-[4,4']bipyrimidinyl-6-one hydrochloride
• 英文别名: 3-methyl-2-[(1S)-5-pyridin-3-yl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-6-pyrimidin-4-ylpyrimidin-4-one;hydrochloride
• 化学式: C₁₉H₁₉N₇O*ClH
• 分子量: 397.867
• InChiKey: KHWXHGCZUSLCPI-SCYKNNLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.52
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  77.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-溴吡啶 、 (1S)-2-(2,5-diazabicyclo[2.2.1]hept-2-yl)-1-methyl-1H-[4,4']bipyrimidinyl-6-one 在 palladium diacetate 、 (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene caesium carbonate 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以26%的产率得到(1S)-1-methyl-2-(5-pyridin-3-yl-2,5-diazabicyclo[2.2.1]hept-2-yl)-1H-[4,4']bipyrimidinyl-6-one hydrochloride
  参考文献：
  名称：

  Substituted pyrimidinyl-2-(diaza-bicyclo-alkyl)-pyrimidone derivatives

  摘要：

  该发明涉及一种由式（I）表示的2-(二氮杂双环烷基)-嘧啶酮衍生物或其盐：其中：R1代表氢原子、C1-6烷基或卤原子；R2代表氢原子、C1-6烷基，可选地被1至4个取自卤原子、羟基或C1-4烷氧基的取代基取代；C1-2全氟烷基、苄基、苯乙基、苄氧羰基、C1-4烷氧羰基、苯环、萘环、喹啉环、邻苯二氮杂环、5,6,7,8-四氢萘环、吡啶环、吲哚环、吡咯环、噻吩环、苯磺酰基、苯甲酰基、吡啶二氮杂环、呋喃环或咪唑环；苄基、苯乙基、苄氧羰基、苯磺酰基、苯甲酰基和环可选地被1至4个取自C1-6烷基、苯环、卤原子、C1-2全氟烷基、C1-3卤代烷基、羟基、C1-4烷氧基、硝基、氰基、氨基、C1-6单烷基氨基基或C2-10二烷基氨基基的取代基取代；R3代表可选地被C1-4烷基、C1-4烷氧基或卤原子取代的2,4或5-嘧啶环；R4代表可选地被羟基、C1-4烷氧基或卤原子取代的C1-4烷基，n代表1或2。该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。

  公开号：

  EP1454910A1

文献信息

• Substituted 2-(diaza-bicyclo-alkyl)-pyrimidone derivatives
  申请人：Lochead Alistair

  公开号：US20060025417A1

  公开（公告）日：2006-02-02

  The invention relates to a 2-(diaza-bicyclo-alkyl)-pyrimidone derivative represented by formula (I): wherein: R1 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom; R2 represents a hydrogen atom, a C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a hydroxyl group, a C 1-4 alkoxy group; a C 1-2 perhalogenated alkyl group, a benzyl group, a phenethyl group, a benzyloxycarbonyl group, a C 1-4 alkoxy carbonyl group, a benzene ring, a naphthalene ring, a quinoline ring, a phthalazine ring, a 5,6,7,8-tetrahydronaphthalene ring, a pyridine ring, an indole ring, a pyrrole ring, a thiophene ring, a benzenesulfonyl group, a benzoyl group, a pyridazine ring, a furan ring and an imidazole ring; each of the benzyl group, the phenethyl group, the benzyloxycarbonyl group, the benzenesulfonyl group, the benzoyl group and the benzene, naphthalene, quinoline, phthalazine, 5,6,7,8-tetrehydronaphthalene, pyridine, indole, pyrrole and thiophene rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a benzene ring, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxyl group, a C 1-4 alkoxy group, a nitro group, a cyano group, an amino group, a C 1-6 monoalkylamino group and a C 2-10 dialkylamino group; R3 represents a 2, 4 or 5-pyrimidine ring or a 2, 3 or 4-pyridine ring, the rings being optionally substituted by a C 1-4 alkyl group, C 1-4 alkoxy group or a halogen atom; R4 represents a C 1-4 alkyl group optionally substituted by a hydroxyl group, a C 1-4 alkoxy group or a halogen atom and n represents 1 or 2; or a salt thereof, or a solvate thereof or a hydrate thereof. 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, such as Alzheimer's disease.

  本发明涉及一种2-(二氮杂双环烷基)-嘧啶酮衍生物，其化学式为(I)：其中：R1表示氢原子、C1-6烷基或卤素原子；R2表示氢原子、C1-6烷基（可选地被1至4个取自卤素原子、羟基、C1-4烷氧基、C1-2全卤代烷基、苄基、苯乙基、苄氧羰基、C1-4烷氧羰基、苯环、萘环、喹啉环、邻二氮杂菲环、5,6,7,8-四氢萘环、吡啶环、吲哚环、吡咯环、噻吩环、苯磺酰基、苯甲酰基、吡嗪环、呋喃环和咪唑环中的一种）；苄基、苯乙基、苄氧羰基、苯磺酰基、苯甲酰基和苯环、萘环、喹啉环、邻二氮杂菲环、5,6,7,8-四氢萘环、吡啶环、吲哚环、吡咯环、噻吩环中的每一种均可选择地被1至4个取自C1-6烷基、苯环、卤素原子、C1-2全卤代烷基、C1-3卤代烷基、羟基、C1-4烷氧基、硝基、氰基、氨基、C1-6单烷基氨基和C2-10双烷基氨基中的一种的取代基所取代；R3表示2、4或5-嘧啶环或2、3或4-吡啶环，环中可选择地被C1-4烷基、C1-4烷氧基或卤素原子取代；R4表示C1-4烷基（可选地被羟基、C1-4烷氧基或卤素原子取代）；n表示1或2；或其盐、溶剂或水合物。本发明还涉及一种药物，包括该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。
• USE OF SUBSTITUTED 2-(DIAZA-BICYCLO-ALKYL)-PYRIMIDONE DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：LOCHEAD Alistair

  公开号：US20070167455A1

  公开（公告）日：2007-07-19

  The invention relates to therapeutic uses of a 2-(diaza-bicyclo-alkyl)-pyrimidone derivative represented by formula (I): Wherein R1, R2, R3, R4 and n are as defined herein. Specifically, the compounds of formula (I) are used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer's disease. The invention relates also to intermediates for the preparation of compound of formula (I).

  本发明涉及一种由式(I)所表示的2-(二氮杂双环烷基)-嘧啶酮衍生物的治疗用途：其中R1、R2、R3、R4和n如所定义。具体地，式(I)化合物用于预防和/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。本发明还涉及制备式(I)化合物的中间体。
• US7211581B2
  申请人：——

  公开号：US7211581B2

  公开（公告）日：2007-05-01
• US7452897B2
  申请人：——

  公开号：US7452897B2

  公开（公告）日：2008-11-18
• Substituted pyrimidinyl-2-(diaza-bicyclo-alkyl)-pyrimidone derivatives
  申请人：SANOFI-SYNTHELABO

  公开号：EP1454910A1

  公开（公告）日：2004-09-08

  The invention relates to a 2-(diaza-bicyclo-alkyl)-pyrimidone derivative represented by formula (I) or a salt thereof: wherein: R1 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R2 represents a hydrogen atom, a C1-6 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a hydroxyl group or a C1-4 alkoxy group; a C1-2 perhalogenated alkyl group, a benzyl group, a phenethyl group, a benzyloxycarbonyl group, a C1-4 alkoxy carbonyl group, a benzene ring, a naphthalene ring, a quinoline ring, a phthalazine ring, a 5,6,7,8-tetrahydronaphthalene ring, a pyridine ring, an indole ring, a pyrrole ring, a thiophene ring, a benzenesulfonyl group, a benzoyl group, a pyridazine ring, a furan ring or an imidazole ring; the benzyl group, the phenethyl group, the benzyloxycarbonyl group, the benzenesulfonyl group, the benzoyl group and the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a benzene ring, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxyl group, a C1-4 alkoxy group, a nitro, a cyano, an amino, a C1-6 monoalkylamino group or a C2-10 dialkylamino group; R3 represents a 2, 4 or 5-pyrimidine ring optionally substituted by a C1-4 alkyl group, C1-4 alkoxy group or a halogen atom; R4 represents a C1-4 alkyl group optionally substituted by a hydroxyl group, a C1-4 alkoxy group or a halogen atom and n represents 1 or 2. 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, such as Alzheimer disease.

  该发明涉及一种由式（I）表示的2-(二氮杂双环烷基)-嘧啶酮衍生物或其盐：其中：R1代表氢原子、C1-6烷基或卤原子；R2代表氢原子、C1-6烷基，可选地被1至4个取自卤原子、羟基或C1-4烷氧基的取代基取代；C1-2全氟烷基、苄基、苯乙基、苄氧羰基、C1-4烷氧羰基、苯环、萘环、喹啉环、邻苯二氮杂环、5,6,7,8-四氢萘环、吡啶环、吲哚环、吡咯环、噻吩环、苯磺酰基、苯甲酰基、吡啶二氮杂环、呋喃环或咪唑环；苄基、苯乙基、苄氧羰基、苯磺酰基、苯甲酰基和环可选地被1至4个取自C1-6烷基、苯环、卤原子、C1-2全氟烷基、C1-3卤代烷基、羟基、C1-4烷氧基、硝基、氰基、氨基、C1-6单烷基氨基基或C2-10二烷基氨基基的取代基取代；R3代表可选地被C1-4烷基、C1-4烷氧基或卤原子取代的2,4或5-嘧啶环；R4代表可选地被羟基、C1-4烷氧基或卤原子取代的C1-4烷基，n代表1或2。该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。