(R) 9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one | 502927-48-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R) 9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one
• 英文别名: 9-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-2-pyrimidin-4-yl-7,8-dihydro-6H-pyrimido[1,2-a]pyrimidin-4-one
• CAS: 502927-48-2
• 化学式: C₁₉H₁₈ClN₅O₂
• 分子量: 383.837
• InChiKey: OZITZBLPTIRHMN-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

文献信息

• Heteroaryl-substituted pyrrole derivates, their preparation and their therapeutic uses
  申请人：Sankyo Company Limited

  公开号：EP1243589A1

  公开（公告）日：2002-09-25

  Compounds of formula (I): [wherein: A is a pyrrole ring; R1 is an optionally substituted phenyl or naphthyl group; R2 is an optionally substituted pyridyl or pyrimidinyl group; R3 represents a group of the formula -X-R4, wherein X is a single bond or an alkenylene group, and R4 is an optionally substituted nitrogen-containing heterocyclyl group; selected from the group consisting of 8-azabicyclo[3.2.1]octenyl, 9-azabicyclo[3.3.1]nonenyl and quinuclidinenyl groups, PROVIDED THAT said substituents R1 and R3 are bonded to the two atoms of said pyrrole ring which are adjacent to the atom of the pyrrole ring to which said substituent R2 is bonded] have excellent inhibitory activity against the production of inflammatory cytokines.

  化合物的结构式（I）：[其中：A为吡咯环；R1为可选取代的苯或萘基团；R2为可选取代的吡啶或嘧啶基团；R3代表具有下述结构的基团-X-R4，其中X为单键或烯基链，R4为可选取代的含氮杂环基团；所选取自8-氮杂双环[3.2.1]辛烯基、9-氮杂双环[3.3.1]壬烯基和喹啉环基团，前提是所述取代基R1和R3连接到所述吡咯环的两个相邻原子，这两个原子与所述取代基R2连接的吡咯环原子相邻]具有出色的抑制炎症细胞因子产生活性。
• 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]Pyrimidin-4-one and 7-Pyrimidinyl-2,3-Dihydroimidazo[1,2-a]Pyrimidin-5(1H)one derivatives
  申请人：SANOFI-SYNTHELABO

  公开号：EP1295884A1

  公开（公告）日：2003-03-26

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof: wherein: 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, a ethenylene group, a ethynylene group, a an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide 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; R1 represents a pyrimidine group;    when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C1-6 alkyl group optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group ; a C 3-6 cycloalkyl group, a C1-4 alkylthio group, a C1-4 alkoxy group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a phenyl ring, a 5,6,7,8-tetrahydronaphthyl ring, a naphthyl ring, a pyridyl ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring ;    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 (optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group), a C3-6 cycloalkyl group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a benzyl group, a phenyl ring, a 5,6,7,8-tetrahydronaphthyl ring, a naphthyl ring, a pyridyl ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring ; R3 and R4 represents each independently a hydrogen atom, C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C1-6 alkyl 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.

  本发明涉及一种由式(I)表示的嘧啶酮衍生物或其盐： 其中： X代表两个氢原子、硫原子、氧原子或C1-2烷基和一个氢原子； Y代表一个键、一个乙烯基、一个乙炔基、一个氧原子、一个硫原子、一个磺酰基、一个亚磺酸基、一个羰基、一个氮原子，该氮原子可选择地被C1-6烷基、苯基或苄基取代；或一个可选择地取代的亚甲基基团； R1代表一个嘧啶基团； 当Y代表一个键、一个可选择地取代的亚甲基基团或一个羰基时，R2代表一个C1-6烷基，可选择地被C6,10芳氧基或C6,10芳基氨基基团取代；一个C3-6环烷基、一个C1-4烷基硫基、一个C1-4烷氧基、一个C1-2全卤代烷基、一个C1-3卤代烷基、一个苯硫基、一个苄基、一个苯环、一个5,6,7,8-四氢萘环、一个萘环、一个吡啶环、一个吡咯环、一个噻吩环、一个呋喃环或一个咪唑环； 当Y代表一个双键、一个三键、一个氧原子、一个硫原子、一个磺酰基、一个亚磺酸基或一个可选择地取代的氮原子时，R2代表一个C1-6烷基（可选择地被C6,10芳氧基或C6,10芳基氨基基团取代）、一个C3-6环烷基、一个C1-2全卤代烷基、一个C1-3卤代烷基、一个苄基、一个苯环、一个5,6,7,8-四氢萘环、一个萘环、一个吡啶环、一个吡咯环、一个噻吩环、一个呋喃环或一个咪唑环； R3和R4各自独立地代表一个氢原子、C1-6烷基、一个羟基、一个C1-4烷氧基或一个卤原子； R5代表一个氢原子、一个C1-6烷基或一个卤原子； 本发明还涉及一种药物，该药物包括上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。
• Substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1h)one derivatives for neurodegenerative disorders
  申请人：——

  公开号：US20040266793A1

  公开（公告）日：2004-12-30

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: X represents two 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, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally; or a methylene group optionally substituted; R1 represents a pyrimidine group optionally substituted; R2 may represent a C 1-6 alkyl group optionally substituted by a C 6,10 aryloxy or a C 6,10 arylamino 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 phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R4 represents each independently a hydrogen atom, C 1-6 alkyl group, a hydroxy group, a C 1- 4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C 1-6 alkyl 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 GSK3&bgr;3 or GSK3&bgr;3 and cdk5/p25, such as Alzheimer disease. 1

  本发明涉及一种由式（I）表示的嘧啶酮衍生物或其盐，其中：X代表两个氢原子，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，氧原子，硫原子，磺酰基，亚磺酸基，羰基，氮原子（可选）或取代的亚甲基基团；R1表示可选取代的嘧啶基团；R2可以代表C1-6烷基，可选地被C6,10芳氧基或C6,10芳基氨基基团取代；C3-6环烷基，C1-4烷基硫基，C1-4烷氧基，C1-2全氟烷基，C1-3卤代烷基，苯硫基，苄基，苯环，茚环，5,6,7,8-四氢萘环，萘环，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环；R3和R4各自独立地表示氢原子，C1-6烷基，羟基，C1-4烷氧基或卤素原子；R5表示氢原子，C1-6烷基或卤素原子。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GSK3β3或GSK3β3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。
• Use of Substituted 2-Pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-A] Pyrimidin-4-one and 7-Pyrimidinyl-2,3-dihydroimidazo[1,2-A] Pyrimidin-5(1H)one Derivatives
  申请人：Gallet Thierry

  公开号：US20080269257A1

  公开（公告）日：2008-10-30

  The invention relates to use of a pyrimidone derivative represented by formula (I) or a salt thereof as therapeutic agents: Wherein m, n, p, X, Y, R1, R2, R3, R4 R5, are as defined herein. The invention specifically 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.

  该发明涉及使用式（I）所表示的嘧啶酮衍生物或其盐作为治疗剂：其中m、n、p、X、Y、R1、R2、R3、R4、R5如本文中所定义。该发明特别涉及一种药物，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异常活性引起的神经退行性疾病，例如阿尔茨海默病。
• Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses
  申请人：Sankyo Company Limited

  公开号：EP1070711A2

  公开（公告）日：2001-01-24

  Compounds of formula (I): [wherein: A is a pyrrole ring; R1 is an optionally substituted aryl or heteroaryl group; R2 is an optionally substituted nitrogen-containing heteroaryl group; R3 represents a group of the formula -X-R4, wherein X is a single bond or an optionally substituted alkylene, alkenylene or alkynylene group, and R4 is a substituted cycloalkyl group, a substituted aryl group, a substituted heterocyclyl group, an optionally substituted nitrogen-containing heterocyclyl group, a substituted heteroaryl group, an optionally substituted nitrogen-containing heteroaryl group, or -NRaRb, wherein each of Ra and Rb is a hydrogen atom or an alkyl, alkenyl, alkynyl, aralkyl or alkylsulfonyl group; PROVIDED THAT said substituents R1 and R3 are bonded to the two atoms of said pyrrole ring which are adjacent to the atom of the pyrrole ring to which said substituent R2 is bonded] have excellent inhibitory activity against the production of inflammatory cytokines.

  式(I)化合物： 其中A 是吡咯环；R1 是任选取代的芳基或杂芳基；R2 是任选取代的含氮杂芳基；R3代表式-X-R4的基团，其中X是单键或任选取代的亚烷基、亚烯基或亚炔基，R4是取代的环烷基、取代的芳基、取代的杂环基、任选取代的含氮杂环基、取代的杂芳基、任选取代的含氮杂芳基，或-NRaRb，其中Ra和Rb各自是氢原子或烷基、烯基、炔基、芳基或烷基磺酰基；前提是所述取代基 R1 和 R3 键合在所述吡咯环的两个原子上，这两个原子与所述取代基 R2 键合的吡咯环原子相邻]对炎症细胞因子的产生具有极佳的抑制活性。