公开(公告)号：EP1295885A1

公开(公告)日：2003-03-26

申请号：EP01402432.7

申请日：2001-09-21

申请人： SANOFI-SYNTHELABO ,  Mitsubishi-Tokyo Pharmaceuticals, Inc.

发明人： Gallet, Thierry ,  Lardenois, Patrick ,  Lochead, Alistair W. ,  Nedelec, Alain ,  Marguerie, Séverine ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P3/10 ,  A61P25/28

CPC分类号： C07D487/04

摘要： 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 hydroxyiminomethylene group, a dioxolan 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 , a hydroxyiminomethylene group, a dioxolan group or a carbonyl group then R2 represents a C 1-6 alkyl group optionally; 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 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 ethenylene group, a 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 optionally substituted by a hydroxy group, a C 6,10 aryloxy or a C 6,10 arylamino group; a C 3-6 cycloalkyl group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a benzyl group, a phenyl ring, a 5,6,7,8-tetrahydronaphthyl ring, a naphthyl ring, a C 6,10 arylamino, 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, a 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; with the proviso that when R3 and R4 represent each a hydrogen atom then R5 is not a hydrogen 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.

摘要翻译： 本发明涉及由式（I）表示的嘧啶酮衍生物或其盐，其中：X表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子; Y表示键，亚乙烯基，亚乙炔基，氧原子，硫原子，磺酰基，亚砜基，羰基，羟基亚氨基亚甲基，二氧戊环，任选取代的氮原子; 或任选取代的亚甲基; R 1表示任选被C 3-6环烷基，C 1-4烷基，C 1-4烷氧基，苄基或卤素原子取代的2,3或4-吡啶基; 当Y表示键时，可以被取代的亚甲基，羟基亚氨基亚甲基，二氧戊环或羰基，则R2表示C1-6烷基; C 3-6环烷基，C 1-4烷硫基，C 1-4烷氧基，C1-2全卤代烷基，C 1-3卤代烷基，苯硫基，苄基，苯环， 5,6,7,8-四氢萘基环，萘环，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环; 当Y表示任选被取代的亚乙烯基，亚乙炔基，氧原子，硫原子，磺酰基，亚砜基或氮原子时，R 2表示任选被羟基取代的C 1-6烷基， C6,10芳氧基或C6,10芳基氨基; C 3-6环烷基，C1-2全卤代烷基，C1-3卤代烷基，苄基，苯环，5,6,7,8-四氢萘基环，萘环，C6， 10芳基氨基，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环; R 3和R 4各自独立地表示氢原子，C 1-6烷基，羟基，C 1-4烷氧基或卤素原子; R5表示氢原子，C1-6烷基或卤素原子; 条件是当R 3和R 4各自表示氢原子时，R 5不是氢原子; 本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/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。

公开(公告)号：EP1184385A1

公开(公告)日：2002-03-06

申请号：EP00402412.1

申请日：2000-09-01

申请人： SANOFI-SYNTHELABO ,  Mitsubishi-Tokyo Pharmaceuticals, Inc.

发明人： Gallet, Thiery ,  Lochead, Alistair ,  Nedelec, Alain ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/00

CPC分类号： C07D487/04

摘要： The invention relates to a dihydroimidazo[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, 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;

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 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy 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 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 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;

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.

摘要翻译： 本发明涉及由式（I）表示的二氢咪唑并[1,2-a]嘧啶酮衍生物或其盐：其中：X表示氢原子，硫原子或氧原子; Y表示键，氧原子，硫原子，磺酰基，亚砜基，羰基，任选取代的氮原子或任选取代的亚甲基; R1表示任选取代的2,3或4-吡啶基; 当Y表示键，亚甲基任意取代或羰基时，则R2表示C1-6烷基，C3-6环烷基，C1-2全卤代烷基，C1-3卤代烷基， C 1-4烷硫基，C 1-4烷氧基，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，萘基或环任选被1至3个取代基取代; 当Y表示氧原子，硫原子，磺酰基，亚砜基或任选被取代的氮原子时，则R2表示C1-6烷基，C3-6环烷基，C1-2全卤代烷基 C 1-3卤代烷基，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，苯基，萘基或环任选被1至3个取代基取代; 并且n表示0至3.本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/或治疗由GSK3β的异常活性引起的神经变性疾病。

公开(公告)号：EP1184384A1

公开(公告)日：2002-03-06

申请号：EP00402411.3

申请日：2000-09-01

申请人： SANOFI-SYNTHELABO ,  Mitsubishi-Tokyo Pharmaceuticals, Inc.

发明人： Lochead, Alistair ,  Marguerie, Séverine ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/00

CPC分类号： A61K31/519 ,  C07D487/04

摘要： The invention relates to a imidazo[1,2- a ]pyrimidone derivative represented by formula (I) or a salt thereof:
wherein:

X represents a bond, a double bond, a triple bond, a methylene group optionally substituted by one or two groups selected from a C 1-6 alkyl group, a hydroxy group and a C 1-4 alcoxy group;
a carbonyl group, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide group or a nitrogen atom being optionally substituted by a C 1-6 alkyl group;
R1 represents a 2, 3 or 4-pyridyl group optionally substituted by a C 1-4 alkyl group, C 1-4 alkoxy group or a halogen atom;
R2 represents a C 1-6 alkyl group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl 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 and the rings being optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group, 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, a cyano, an amino, a C 1-6 monoalkylamino group or a C 2-10 dialkylamino group;
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.

摘要翻译： 本发明涉及由式（I）表示的咪唑并[1,2-a]嘧啶酮衍生物或其盐：其中：X表示键，双键，三键，任选被一个或两个基团取代的亚甲基 选自C 1-6烷基，羟基和C 1-4烷氧基; 羰基，氧原子，硫原子，磺酰基，亚砜基或任选被C 1-6烷基取代的氮原子; R1表示任选被C 1-4烷基，C 1-4烷氧基或卤素原子取代的2,3或4-吡啶基; R2表示C1-6烷基，C1-2全卤代烷基，C1-3卤代烷基，苄基，苯环，吡啶环，吲哚环，吡咯环，噻吩环， 呋喃环或咪唑环，苄基和环任选被1至3个选自C 1-6烷基，卤素原子，C 1-2-2全卤代烷基，C 1-3卤代烷基， 羟基，C 1-4烷氧基，硝基，氰基，氨基，C 1-6单烷基氨基或C 2-10二烷基氨基; 并且n表示0至3.本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/或治疗由GSK3β的异常活性引起的神经变性疾病。

公开(公告)号：EP1295884A1

公开(公告)日：2003-03-26

申请号：EP01402431.9

申请日：2001-09-21

申请人： SANOFI-SYNTHELABO ,  Mitsubishi-Tokyo Pharmaceuticals, Inc.

发明人： Gallet, Thierry ,  Lardenois, Patrick ,  Lochead, W. Alistair ,  Nedelec, Alain ,  Marguerie, Séverine ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/28

CPC分类号： C07D487/04

摘要： 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, 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 C 1-6 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 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 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 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 1-2 perhalogenated alkyl group, a C 1-3 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, 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 GSK3β or GSK3β and cdk5/p25, such as Alzheimer disease.

摘要翻译： 本发明涉及由式（I）表示的嘧啶酮衍生物或其盐：其中：X表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子; Y表示键，亚乙烯基，亚乙炔基，氧原子，硫原子，磺酰基，亚砜基，羰基，任选被C 1-6烷基取代的氮原子，苯基 或苄基; 或任选取代的亚甲基; R1代表嘧啶基团; 当Y代表键，亚甲基任意取代或羰基时，则R2表示任选被C 6,10芳氧基或C 6,10芳基氨基取代的C 1-6烷基; C 3-6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，苯硫基，苄基，苯环， 5,6,7,8-四氢萘基环，萘环，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环; 当Y表示双键，三键，氧原子，硫原子，磺酰基，亚砜基或任选被取代的氮原子时，R 2表示C 1-6烷基（任选被C 6,10 芳氧基或C6,10芳基氨基），C3-6环烷基，C1-2全卤代烷基，C1-3卤代烷基，苄基，苯环，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; 本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/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。

公开(公告)号：EP1184383A1

公开(公告)日：2002-03-06

申请号：EP00402410.5

申请日：2000-09-01

申请人： SANOFI-SYNTHELABO ,  Mitsubishi-Tokyo Pharmaceuticals, Inc.

发明人： Almario-Garcia, Antonio ,  Li, Adrien-Tak ,  Lochead, Alistair ,  Marguerie, Séverine ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/00

CPC分类号： C07D487/04

摘要： 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 C 1-6 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 C 1-4 alkyl group, a C 1-4 alkoxy group or a halogen atom;

when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C 1-6 alkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy group, a C 3-6 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 C 1-6 alkyl group, a C 3-6 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.

摘要翻译： 本发明涉及由式（I）表示的6,7,8,9-四氢嘧啶并嘧啶酮衍生物或其盐：其中：X表示氢原子，硫原子或氧原子; Y表示键，双键，三键，氧原子，硫原子，磺酰基，亚砜基，羰基，任选被C 1-6烷基取代的氮原子，苯基或 苄基; 或任选被一个或两个取代基取代的亚甲基; R1表示任选被C 1-4烷基，C 1-4烷氧基或卤素原子取代的2,3或4-吡啶基; 当Y表示键，亚甲基任意取代或羰基时，则R2表示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，萘基或环任选被1至3个取代基取代; 当Y表示双键时，任选被取代的三键，氧原子，硫原子，磺酰基，亚砜基或氮原子，则R2表示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，萘基或环任选地 被1-3个取代基取代; 并且n表示0至3.本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/或治疗由GSK3β的异常活性引起的神经变性疾病。

公开(公告)号：EP1348708A1

公开(公告)日：2003-10-01

申请号：EP02290486.6

申请日：2002-02-28

申请人： SANOFI-SYNTHELABO ,  MITSUBISHI PHARMA CORPORATION

发明人： Lochead, Alistair, W. ,  Nedelec, Alain ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  C07D519/00 ,  A61K31/517 ,  A61P25/00

CPC分类号： C07D487/04

摘要： 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 or a methylene group optionally substituted by one or two groups chosen from a C 1-6 alkyl group, a hydroxy group or a C 1-4 alkoxy group;
R1 represents a 2, 4 or 5-pyrimidine ring optionally;
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

R3 represents a hydrogen atom, a C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom;
R4 represents a hydrogen atom, a C 1-6 alkyl group, a C 1-4 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.

摘要翻译： 本发明涉及由式（I）表示的嘧啶酮衍生物或其盐，其中：X表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子; Y表示任选被一个或两个选自C 1-6烷基，羟基或C 1-4烷氧基的基团取代的键，亚乙烯基，亚乙炔基或亚甲基; R1代表任选的2,4或5-嘧啶环; R 2表示具有1-4个选自氧原子，硫原子和氮原子并且具有5-9个碳原子的杂原子的杂环二环，式 R 3表示氢原子，C 1-6烷基 ，羟基，C 1-4烷氧基或卤素原子; R4表示氢原子，C1-6烷基，C1-4烷氧基或卤素原子; 本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/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。

公开(公告)号：EP1340758A1

公开(公告)日：2003-09-03

申请号：EP02290485.8

申请日：2002-02-28

申请人： SANOFI-SYNTHELABO ,  MITSUBISHI PHARMA CORPORATION

发明人： Lochhead, Alistair, W. ,  Nedelec, Alain ,  Saady, Mourad ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  C07D519/00 ,  A61K31/519 ,  A61P25/00

CPC分类号： C07D487/04

摘要： 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 or a methylene group optionally substituted;
R1 represents a 2, 3 or 4-pyridine 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

R3 represents a hydrogen atom, a C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom;
R4 represents a hydrogen atom, a C 1-6 alkyl group, a C 1-4 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.

摘要翻译： 本发明涉及由式（I）表示的嘧啶酮衍生物或其盐，其中：X表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子; Y表示键，亚乙烯基，亚乙炔基或任选取代的亚甲基; R1表示任选取代的2,3或4-吡啶环; R 2表示具有1-4个选自氧原子，硫原子和氮原子并且具有5-9个碳原子的杂原子的杂环二环，式 R 3表示氢原子，C 1-6烷基 ，羟基，C 1-4烷氧基或卤素原子; R 4表示氢原子，C 1-6烷基，C 1-4烷氧基或卤素原子; 本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/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。

公开(公告)号：EP1454910A1

公开(公告)日：2004-09-08

申请号：EP03290570.5

申请日：2003-03-07

申请人： SANOFI-SYNTHELABO ,  Mitsubishi Pharma Corporation

发明人： Lochead, Alistair W. ,  Saady, Mourad ,  Slowinski, Franck ,  Yaiche, Philippe

IPC分类号： C07D487/08 ,  A61K31/506 ,  A61P25/28 ,  A61P35/00

CPC分类号： C07D487/08

摘要： 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 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 or 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 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 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, a cyano, an amino, a C 1-6 monoalkylamino group or a C 2-10 dialkylamino group;
R3 represents a 2, 4 or 5-pyrimidine ring 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.

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.

摘要翻译： 本发明涉及由式（I）表示的2-（二氮杂双环烷基） - 嘧啶酮衍生物或其盐：其中：R1表示氢原子，C1-6烷基或卤素原子; R2表示氢原子，任选被1至4个选自卤素原子，羟基或C 1-4烷氧基的取代基取代的C 1-6烷基; C1-2全卤代烷基，苄基，苯乙基，苄氧基羰基，C1-4烷氧基羰基，苯环，萘环，喹啉环，酞嗪环，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，哒嗪环，呋喃环或咪唑环; 苄基，苯乙基，苄氧基羰基，苯磺酰基，苯甲酰基和环任选被1〜4个选自C 1-6烷基，苯环，卤素原子，C1- 2个全卤代烷基，C1-3卤代烷基，羟基，C1-4烷氧基，硝基，氰基，氨基，C1-6单烷基氨基或C2-10二烷基氨基; R3表示任选被C 1-4烷基，C 1-4烷氧基或卤素原子取代的2,4或5-嘧啶环; R 4表示任选被羟基，C 1-4烷氧基或卤素原子取代的C 1-4烷基，n表示1或2.本发明还涉及包含所述衍生物或盐的药物 作为活性成分，其用于预防和/或治疗由GSK3β的异常活性如阿尔茨海默病引起的神经变性疾病。

公开(公告)号：EP1340761A1

公开(公告)日：2003-09-03

申请号：EP02290489.0

申请日：2002-02-28

申请人： SANOFI-SYNTHELABO ,  MITSUBISHI PHARMA CORPORATION

发明人： Gallet, Thierry ,  Lardenois, Patrick ,  Lochead, Alistair, W. ,  Marguerie, Severine ,  Nedelec, Alain ,  Saady, Mourad ,  Slowinski, Franck ,  Yaiche, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/00

CPC分类号： C07D487/04

摘要： 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 hydroxyiminomethylene group, a dioxolan group, a nitrogen atom being optionally substituted; or a methylene group optionally substituted;
R1 represents a 2, 3 or 4-pyridine ring optionally substituted;
R2 may represent a C 1-6 alkyl group optionally; 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 phenyl ring, a 5,6,7,8-tetrahydronaphthyl ring, a naphthyl 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, a 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; with the proviso that when R3 and R4 represent each a hydrogen atom then R5 is not a hydrogen 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.

摘要翻译： 本发明涉及由式（I）表示的嘧啶酮衍生物或其盐，其中：X表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子; Y表示键，亚乙烯基，亚乙炔基，氧原子，硫原子，磺酰基，亚砜基，羰基，羟基亚氨基亚甲基，二氧戊环，任选取代的氮原子; 或任选取代的亚甲基; R1表示任选取代的2,3或4-吡啶环; 任选地，R 2可以表示C 1-6烷基; C 3-6环烷基，C 1-4烷硫基，C 1-4烷氧基，C1-2全卤代烷基，C 1-3卤代烷基，苯硫基，苄基，苯环， 5,6,7,8-四氢萘基环，萘环，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环; R 3和R 4各自独立地表示氢原子，C 1-6烷基，羟基，C 1-4烷氧基或卤素原子; R5表示氢原子，C1-6烷基或卤素原子; 条件是当R 3和R 4各自表示氢原子时，R 5不是氢原子。 本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/或治疗由GSK3β或GSk3β和cdk5 / p25的异常活性引起的神经变性疾病的预防和/或治疗，例如 阿尔茨海默病。

公开(公告)号：EP1460076A1

公开(公告)日：2004-09-22

申请号：EP03290728.9

申请日：2003-03-21

申请人： SANOFI-SYNTHELABO ,  Mitsubishi Pharma Corporation

发明人： Lochead, Alistair W. ,  Saady, Mourad ,  Slowinski, Franck ,  Yaiche, Philippe

IPC分类号： C07D487/04

CPC分类号： A61K31/519 ,  C07D487/04

摘要： The invention relates to a substituted-pyrimidone derivative represented by formula (I) or a salt thereof:
wherein:

X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom;
Y represents a bond, a carbonyl group, a methylene group optionally substituted;
R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the rings being optionally substituted;
R2 represents a phenyl group or a naphthalene ring; the phenyl group and the naphthalene ring being optionally substituted;
R3 represents a hydrogen atom or a C 1-6 alkyl group;
R4 represents a C 1-2 perhalogenated alkyl group or a C 1-3 halogenated alkyl group;
R5 represents a hydrogen atom; a C 1-6 alkyl group or a halogen atom;
n represents 0 to 3; and p+q=0-3.

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, such as Alzheimer disease.

摘要翻译： 本发明涉及由式（I）表示的取代嘧啶酮衍生物或其盐：其中：X表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子; Y表示键，羰基，任选取代的亚甲基; R1表示2,3或4-吡啶环或2,4或5-嘧啶环，该环任选被取代; R2表示苯基或萘环; 苯基和萘环任选被取代; R3表示氢原子或C1-6烷基; R4表示C1-2全卤代烷基或C1-3卤代烷基; R5表示氢原子; C 1-6烷基或卤素原子; n表示0〜3; 和p + q = 0-3。 本发明还涉及包含所述衍生物或其盐作为活性成分的药物，其用于预防和/或治疗由GSK3β的异常活性如阿尔茨海默病引起的神经变性疾病。