公开(公告)号：EP2162443A2

公开(公告)日：2010-03-17

申请号：EP08807106.3

申请日：2008-05-14

申请人： Sanofi-Aventis ,  Mitsubishi Tanabe Pharma Corporation

发明人： CHEREZE, Nathalie ,  GALLET, Thierry ,  LOCHEAD, Alistair ,  SAADY, Mourad ,  VERONIQUE, Corinne ,  YAICHE, Philippe

IPC分类号： C07D239/38 ,  C07D471/04 ,  A61P35/00

CPC分类号： C07D403/14 ,  C07D239/38 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04

摘要： A pyrimidone derivative represented by Formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: Formula (I). The compounds (I) are suitable for the treatment of neurodegenerative diseases.

摘要翻译： 由式（I）表示的嘧啶酮衍生物或其盐或其溶剂合物或其水合物：化合物（I）适用于治疗神经变性疾病。

公开(公告)号：EP1957492A2

公开(公告)日：2008-08-20

申请号：EP06847275.2

申请日：2006-11-21

申请人： sanofi-aventis ,  Mitsubishi Tanabe Pharma Corporation

发明人： CHEREZE, Nathalie ,  LOCHEAD, Alistair ,  SAADY, Mourad ,  SLOWINSKI, Franck ,  YAICHE, Philippe

IPC分类号： C07D471/04 ,  A61K31/519

CPC分类号： C07D239/00 ,  C07D471/04

摘要： A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: wherein: Y represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C1-3 alkyl group, a sulphur atom, a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted; R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted; R3 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R4 represents a hydrogen atom or a C-1-6 alkyl group; R5 represents a hydrogen atom, a C1-6 alkyl group optionally substituted; R6 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R7 represents a hydrogen atom or a C1-6 alkyl group; n represents 0 to 3; m represents 0 to 1; o represents 0 to 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： 由式（I）表示的嘧啶酮衍生物或其盐或其溶剂合物或其水合物：其中：Y表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子 ; Z表示键，氧原子，被氢原子或C 1-3烷基取代的氮原子，硫原子，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代表苯环或萘环; 所述环任选被取代; R 3表示氢原子，C 1-6烷基或卤素原子; R 4表示氢原子或C 1-6烷基; R5表示氢原子，C 1-6烷氧基羰基或任选取代的C 1-6烷基; R6表示氢原子，C 1-6烷基或卤素原子; R 7表示氢原子或C 1-6烷基; n表示0〜3; m表示0〜1; o表示0至2.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GSK3 2异常活动引起的神经变性疾病，例如阿尔茨海默病 。

公开(公告)号：EP1608654A2

公开(公告)日：2005-12-28

申请号：EP04721906.8

申请日：2004-03-19

申请人： Sanofi-Aventis ,  Mitsubishi Pharma Corporation

发明人： LOCHEAD, Alistair ,  SAADY, Mourad ,  SLOWINSKI, Franck ,  YAICHE, Philippe

IPC分类号： C07D487/04 ,  A61P25/00

CPC分类号： A61K31/519 ,  C07D487/04

摘要： The invention relates to substituted-pyrimidone derivatives represented by formula (I) or a salt thereof: wherein: X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 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 C1-6 alkyl group; R4 represents a phenyl group, a pyridinyl group or a naphthalene ring, the groups and the ring being optionally substituted; R5 represents a hydrogen atom, a C1-6 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表示苯基，吡啶基或萘环，所述基团和所述环任选被取代; R5表示氢原子，C1-6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。

公开(公告)号：EP1603910A1

公开(公告)日：2005-12-14

申请号：EP04717644.1

申请日：2004-03-05

申请人： Sanofi-Aventis ,  Mitsubishi Pharma Corporation

发明人： LOCHEAD, Alistair ,  SAADY, Mourad ,  SLOWINSKI, Franck ,  YAICHE, Philippe

IPC分类号： C07D471/08 ,  C07D487/08 ,  A61K31/4995 ,  A61P25/28

CPC分类号： A61K31/506 ,  C07D401/14 ,  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 C1-6 alkyl group or a halogen atom; R2 represents a hydrogen atom, a C1-6 alkyl group optionally substituted; 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; R3 represents a 2, 4 or 5-pyrimidine ring or a 2, 3 or 4-pyridine ring, the rings being optionally substituted; R4 represents a C 1-4 alkyl group 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：其中：R 1表示氢原子，C 1-6烷基或卤素原子 ; R 2表示氢原子，任选被1至4个选自卤素原子，羟基，C 1-4烷氧基的取代基取代的C 1-6烷基 组; C 1〜12个全卤代烷基，苄基，苯乙基，苄氧基羰基，C 1-4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， 呋喃环和咪唑环; 苄基，苯乙基，苄氧基羰基，苯磺酰基，苯甲酰基和苯，萘，喹啉，酞嗪，5,6,7,8-四氢萘，吡啶，吲哚，吡咯和噻吩环为 任选被1至4个选自C 1-6烷基，苯环，卤素原子，C 1-12全卤化烷基的取代基取代，C 1-3个卤代烷基，羟基，C 1-4烷氧基，硝基，氰基，氨基，C 1 -C 4烷氧基， 1-6个单烷基氨基和C 2-10 - 二烷基氨基; R3表示2,4或5-嘧啶环或2,3或4-吡啶环，该环任选被C 1-4烷基取代，C 1-4 烷氧基或卤素原子; R4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; 或其盐，或其溶剂合物或其水合物。 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如阿尔茨海默病异常活动引起的神经变性疾病。

公开(公告)号：EP1430057B1

公开(公告)日：2005-08-31

申请号：EP02785157.5

申请日：2002-09-19

申请人： Sanofi-Aventis ,  Mitsubishi Pharma Corporation

发明人： GALLET, Thierry ,  LARDENOIS, Patrick ,  LOCHEAD, Alistair ,  MARGUERIE, Séverine ,  NEDELEC, Alain ,  SAADY, Mourad ,  SLOWINSKI, Franck ,  YAICHE, Philippe

IPC分类号： C07D487/04

CPC分类号： A01N43/90 ,  C07D213/50 ,  C07D213/60 ,  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 sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group an oxygen atom, a sulfur 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; or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring optionally substituted; R2 may represent a C1-6 alkyl group optionally; a C3-6 cycloalkyl group, a C1-4 alkythio 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 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 represent, each independently, a hydrogen atom, a 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; 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： 本发明涉及式（IV）的3-酮酯，其中R 1表示任选被C 3-6环烷基取代的2,3或4-吡啶环，C 1-4烷基， C 1-4烷氧基，苄基或卤素原子，R 5为卤素原子，R为烷基。

公开(公告)号：EP2321314A2

公开(公告)日：2011-05-18

申请号：EP09769672.8

申请日：2009-06-25

申请人： Mitsubishi Tanabe Pharma Corporation ,  Sanofi-Aventis

发明人： LOCHEAD, Alistair ,  SAADY, Mourad ,  YAICHE, Philippe

IPC分类号： C07D471/04 ,  A61K31/519 ,  A61P25/00

CPC分类号： C07D471/04 ,  A61K31/519 ,  Y02A50/411

摘要： Pyrimidone derivatives of formula (I) wherein: R1 represents a 4-pyridine ring; R2 represents a hydrogen atom; R3 represents a hydrogen atom; R4 represents : a hydrogen atom; a phenyl ring, this ring being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a halogen atom, a C 1-2 halogenated alkyl group, a hydroxyl group, a C 1-6 alkoxy group, a C 1-2 halogenated alkoxy group, R5 represents a hydrogen atom, a C 1-6 alkyl group, a 4-pyridine group, a phenyl group, these groups being optionally substituted, R6 represents a hydrogen atom, a C 1-6 alkyl group, a benzyloxy group, a phenyl C 1-6 alkyl group, these groups being optionally substituted, in form of a free base or of an addition salt with an acid. Use in therapeutic.

摘要翻译： 式（I）的嘧啶酮衍生物其中：R1表示4-吡啶环; R2表示氢原子; R3表示氢原子; R4表示：氢原子; 苯环，该环任选被1至4个选自C 1-6烷基，卤素原子，C 1-2卤代烷基，羟基，C 1-6烷氧基，C 1-6烷氧基， C 1-2卤代烷氧基，R 5表示氢原子，C 1-6烷基，4-吡啶基，苯基，这些基团任选被取代，R 6表示氢原子，C 1-6烷基 基团，苄氧基，苯基C 1-6烷基，这些基团任选被取代，形式为游离碱或与酸形成的加成盐。 用于治疗。

公开(公告)号：EP2307416A2

公开(公告)日：2011-04-13

申请号：EP09769674.4

申请日：2009-06-25

申请人： Mitsubishi Tanabe Pharma Corporation ,  Sanofi-Aventis

发明人： ALMARIO GARCIA , Antonio ,  LOCHEAD, Alistair ,  SAADY, Mourad ,  YAICHE, Philippe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/00 ,  A61P35/00 ,  C07D519/00

CPC分类号： A01N43/54 ,  C07D487/04 ,  C07D519/00

摘要： Substituted Tricyclic Derivatives, Formula (I) wherein: Z represents a bond, a carbonyl group, a methylene group optionally substituted by one or two groups chosen from a Ci-6 alkyl group, a hydroxyl group, a C-ι-6 alkoxy group; R1 represents a 4-pyridine ring, a 4-pyrimidine ring; R2 represents a hydrogen atom; R3 represents: a hydrogen atom; a phenyl or a naphthyl group, these groups being optionally substituted, a 5, 6 or 5-6 membered heteroaromatic group, this group being optionally substituted, n represents 0 to 3; m represents 0 to 1, in form of a free base or of an addition salt with an acid. Use in therapeutic

公开(公告)号：EP2247599A1

公开(公告)日：2010-11-10

申请号：EP09706539.5

申请日：2009-01-27

申请人： Sanofi-Aventis ,  Mitsubishi Tanabe Pharma Corporation

发明人： FAYOL, Aude ,  LOCHEAD, Alistair ,  SAADY, Mourad ,  VACHE, Julien ,  YAICHE, Philippe

IPC分类号： C07D498/04 ,  A61K31/33 ,  A61P25/00

CPC分类号： C07D498/04

摘要： A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: wherein: Y represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C1-3 alkyl group, a sulphur atom, a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, a C1-2 perhalogenated alkyl group or an amino group; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C1-6 alkyl group, a C1-6 alkoxy group or a halogen atom; R2 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R3 represents a benzene ring or a naphthalene ring; the rings being optionally substituted R4 represents a hydrogen atom or a C1-6 alkyl group; and n represents 0 to 3 and their therapeutic use.

摘要翻译： 式（I）代表的嘧啶酮衍生物或其盐，或其溶剂合物或其水合物：其中：Y代表两个氢原子，硫原子，氧原子或C1-2烷基和氢原子; Z表示键，氧原子，被氢原子或C1-3烷基取代的氮原子，硫原子，任选被选自C1-6烷基，羟基 基团，C1-6烷氧基，C1-2全卤代烷基或氨基; R1代表2,3或4-吡啶环或2,4或5-嘧啶环，所述环任选被C1-6烷基，C1-6烷氧基或卤素原子取代; R2代表氢原子，C1-6烷基或卤素原子; R3代表苯环或萘环; 该环任选被取代; R4表示氢原子或C1-6烷基; n代表0至3及其治疗用途。

公开(公告)号：EP2238140A2

公开(公告)日：2010-10-13

申请号：EP09705869.7

申请日：2009-01-27

申请人： Sanofi-Aventis ,  Mitsubishi Tanabe Pharma Corporation

发明人： FAYOL, Aude ,  LOCHEAD, Alistair ,  SAADY, Mourad ,  VACHE, Julien ,  YAICHE, Philippe

IPC分类号： C07D487/04

CPC分类号： C07D487/04 ,  C07D519/00

摘要： A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof, Formula (I): wherein: Y represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C
1-2 alkyl group and a hydrogen atom; Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C
1-3 alkyl group, a sulphur atom, a methylene group optionally substituted by one or two groups chosen from a C
1-6 alkyl group, a hydroxyl group, a C
1-6 alkoxy group, a C
1-2 perhalogenated alkyl group or an amino group; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C
1-6 alkyl group, a C
1-6 alkoxy group or a halogen atom; R2 represents a hydrogen atom, a C
1-6 alkyl group or a halogen atom; R3 represents a 4-15 membered heterocyclic group, this group being optionally substituted R4 represents a hydrogen atom, a C
1-6 alkyl group optionally substituted by 1 to 4 substituents R5 represents a hydrogen atom or a C
1-6 alkyl group; and n represents 0 to 3 and their therapeutic use.

摘要翻译： 由式（I）表示的嘧啶酮衍生物或其盐或其溶剂合物或其水合物：其中：Y表示两个氢原子，硫原子，氧原子或C 1-2烷基和氢原子 ; Z表示键，氧原子，被氢原子或C 1-3烷基取代的氮原子，硫原子，任选被一个或两个选自C 1-6烷基的基团取代的亚甲基， 羟基，C 1-6烷氧基，C 1-2全卤代烷基或氨基; R1表示2,3或4-吡啶环或2,4或5-嘧啶环，该环任选被C 1-6烷基，C 1-6烷氧基或卤素原子取代; R 2表示氢原子，C 1-6烷基或卤素原子; R3表示4-15元杂环基，该基团任选被取代，R 4表示氢原子，任选被1至4个取代基取代的C 1-6烷基表示氢原子或C 1-6烷基; n表示0〜3，其治疗用途。

公开(公告)号：EP2160388A2

公开(公告)日：2010-03-10

申请号：EP08807123.8

申请日：2008-05-14

申请人： Sanofi-Aventis ,  Mitsubishi Tanabe Pharma Corporation

发明人： LOCHEAD, Alistair ,  SAADY, Mourad ,  VERONIQUE, Corinne ,  YAICHE, Philippe

IPC分类号： C07D403/04

CPC分类号： C07D403/04 ,  A61K9/0019 ,  A61K9/2018 ,  A61K9/4858 ,  C07D413/14 ,  Y02A50/411

摘要： A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: wherein X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C 1-3 alkyl group, a sulphur atom, a methylene group optionally substituted by one or two groups chosen from a C 1-6 alkyl group, a hydroxyl group, a C 1-6 alkoxy group, a C 1-2 perhalogenated alkyl group or an amino group; R1 represents a 2, 4 or 5-pyrimidine ring or a 4-pyridine ring, the ring being optionally substituted by a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom; R2 represents a benzene ring, a naphthalene ring or a benzyl group ; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, C 3-7 cycloalkyl group, a C 3-7 cycloalkyl-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, an heteroaryl group optionally substituted by a C 1-6 alkyl group, C 3-7 cycloalkyl group, a C 3-7 cycloalkyl-C 1-6 alkyl group, C 1-6 alkoxy group optionally substituted by a C 3-5 cycloalkyl group, a C 1-2 perhalogenated alkoxy group, a C 1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C 1-6 monoalkylamino group or a C 2-12 dialkylamino group, an acetoxy group or an aminosulfonyl group; R3 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom; R4 represents a hydrogen atom or a C 1-6 alkyl group; R5 represents a hydrogen atom, a C 1-6 alkyl group; R6 represents a hydrogen atom, a C 1-6 alkyl group; R7 represents a hydrogen atom or a C 1-6 alkyl group; n represents 0 to 3 and m represents 1 in the form of a free base or of an addition salt with an acid.

摘要翻译： 由式（I）表示的嘧啶酮衍生物或其盐或其溶剂合物或其水合物：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; Z表示键，氧原子，被氢原子或C 1-3烷基取代的氮原子，硫原子，任选被一个或两个选自C 1-6烷基的基团取代的亚甲基， 羟基，C 1-6烷氧基，C 1-2全卤代烷基或氨基; R1表示2,4或5-嘧啶环或4-吡啶环，该环任选被C 1-6烷基，C 1-6烷氧基或卤素原子取代; R2表示苯环，萘环或苄基; 该环任选被1至4个选自C 1-6烷基，C 3-7环烷基，C 3-7环烷基-C 1-6烷基，卤素原子，C 1-2 全卤代烷基，C 1-3卤代烷基，羟基，任选被C 1-6烷基取代的杂芳基，C 3-7环烷基，C 3-7环烷基-C 1-6烷基 基团，任选被C 3-5环烷基取代的C 1-6烷氧基，C 1-2全卤代烷氧基，C 1-6烷基磺酰基，硝基，氰基，氨基，C 1-6 单烷基氨基或C 2-12二烷基氨基，乙酰氧基或氨基磺酰基; R 3表示氢原子，C 1-6烷基或卤素原子; R 4表示氢原子或C 1-6烷基; R5表示氢原子，C 1-6烷基; R6表示氢原子，C 1-6烷基; R 7表示氢原子或C 1-6烷基; n表示0〜3，m表示1以游离碱或与酸的加成盐形式的1。