公开(公告)号：US07476674B2

公开(公告)日：2009-01-13

申请号：US12029008

申请日：2008-02-11

申请人： Frederic Galli ,  Odile Leclerc ,  Alistair Lochead ,  Julien Vache

发明人： Frederic Galli ,  Odile Leclerc ,  Alistair Lochead ,  Julien Vache

IPC分类号： C07D403/04 ,  C07D403/14 ,  A61K31/501

CPC分类号： C07D471/18

摘要： The invention relates to compounds having general formula (I), wherein R is as defined herein. The invention also relates to acid addition salt, a hydrate or a solvate of compounds of formula (I). The invention further relates to the method of preparing said compounds and to the use of same in therapeutics.

摘要翻译： 本发明涉及具有通式（I）的化合物，其中R如本文所定义。 本发明还涉及式（I）化合物的酸加成盐，水合物或溶剂合物。 本发明还涉及制备所述化合物的方法及其在治疗中的用途。

公开(公告)号：US07452897B2

公开(公告)日：2008-11-18

申请号：US11693345

申请日：2007-03-29

申请人： Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

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

IPC分类号： A61K31/506 ,  A61K31/444 ,  A61P3/10 ,  A61P25/28 ,  C07D401/14 ,  C07D403/14

CPC分类号： A61K31/506 ,  C07D401/14 ,  C07D487/08

摘要： 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).

摘要翻译： 本发明涉及由式（I）表示的2-（二氮杂 - 双环烷基） - 嘧啶酮衍生物的治疗用途：其中R1，R2，R3，R4和n如本文所定义。 具体来说，式（I）化合物可用于预防和/或治疗由诸如阿尔茨海默病的GSK3β异常活动引起的神经变性疾病。 本发明还涉及制备式（I）化合物的中间体。

公开(公告)号：US20080081820A1

公开(公告)日：2008-04-03

申请号：US11866687

申请日：2007-10-03

申请人： Nathalie CHEREZE ,  Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

发明人： Nathalie CHEREZE ,  Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

IPC分类号： A61K31/527 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P3/04

CPC分类号： A61K31/527 ,  A61K31/397 ,  C07D487/04 ,  Y02P20/142

摘要： The invention relates to a dihydrospiro-[cycloalkylamine]-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, 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 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, a C1-4 alkoxy carbonyl group, a C1-5 alkyl group optionally substituted; o and m represent 1 to 2; n represents 0 to 3; p represents 0 to 2; and q 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： 本发明涉及由式（I）表示的二氢螺环 - [环烷基胺] - 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; R4表示氢原子，C 1-4烷氧基羰基，任选取代的C 1-5烷基; o和m表示1〜2; n表示0〜3; p表示0〜2; 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，所述活性成分用于预防和/或治疗由GSK3β如异常活动引起的神经变性疾病，例如阿尔茨海默氏症 疾病。

公开(公告)号：US07294632B2

公开(公告)日：2007-11-13

申请号：US11220999

申请日：2005-09-07

申请人： Pascal George ,  Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

发明人： Pascal George ,  Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

IPC分类号： A61P25/28 ,  C07D243/04 ,  C07D487/20

CPC分类号： C07D487/10

摘要： The invention relates to a dihydrospiro-[cycloalkyl]-pyrimidone derivative represented by formula (I) or a salt thereof: wherein X, Y, R1, R2, R3, m, n, p and q are as described herein. 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）表示的二氢螺环 - [环烷基] - 嘧啶酮衍生物或其盐：其中X，Y，R 1，R 2，R 3，m，n，p和q如本文所述。 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，所述活性成分用于预防和/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：US20060035910A1

公开(公告)日：2006-02-16

申请号：US11224873

申请日：2005-09-13

申请人： Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

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

IPC分类号： A61K31/519 ,  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, Y, R1, R2, R3, R4, R5, n, p and q are as described herein. 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，Y，R 1，R 2，R 3，R 4，R 5，n，p和q如本文所述。 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，所述活性成分用于预防和/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：US20060035885A1

公开(公告)日：2006-02-16

申请号：US11225218

申请日：2005-09-13

申请人： Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

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

IPC分类号： A61K31/55 ,  A61K31/519 ,  C07D487/04

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, Y, R1, R2, R3, R4, R5, n, p and q are as defined herein. 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.

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，Y，R 1，R 2，R 3，R 4，R 5，n，p和q如本文所定义。 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：US20060025417A1

公开(公告)日：2006-02-02

申请号：US11219923

申请日：2005-09-06

申请人： Alistair Lochead ,  Mourad Saady ,  Franck Slowinski ,  Philippe Yaiche

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

IPC分类号： A61K31/513 ,  C07D403/14

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): 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, 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 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 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 group, a cyano group, an amino group, a C1-6 monoalkylamino group and a C2-10 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 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; 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.

公开(公告)号：US06987106B1

公开(公告)日：2006-01-17

申请号：US09937045

申请日：2000-03-21

申请人： Thierry Gallet ,  Samir Jegham ,  Patrick Lardenois ,  Alistair Lochead ,  Alain Nedelec

发明人： Thierry Gallet ,  Samir Jegham ,  Patrick Lardenois ,  Alistair Lochead ,  Alain Nedelec

IPC分类号： A61P25/00 ,  A61K31/551 ,  C07D471/08

CPC分类号： C07D471/08

摘要： Compounds of general formula in which X represents an oxygen atom or a group of formula NZ in which Z represents a hydrogen atom or an alkyl group, n represents a number 0, 1 or 2, and R1, R2, R3, R4 and R5 each represent a hydrogen or halogen atom or a trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, alkyl, alkoxy, phenoxy or phenyl group optionally substituted with a halogen atom or a trifluoromethyl, cyano, hydroxyl, alkyl or alkoxy group, or alternatively R2 and R3 together form a group of formula —OCH2O— or —CH2CH2CH2CH2—. Application in therapy.

摘要翻译： 其中X表示氧原子或式NZ的基团的通式的化合物，其中Z表示氢原子或烷基，n表示数字0,1或2，R 1， R 2，R 3，R 4和R 5各自表示氢或卤素原子或三氟甲基， 三氟甲氧基，氰基，羟基，烷基，烷氧基，苯氧基或苯基，任选被卤素原子或三氟甲基，氰基，羟基，烷基或烷氧基取代，或者R 2和R 3 一起形成式-OCH 2 O或-CH 2 CH 2 CH 2 CH 2的基团 > CH 2 - 。 应用于治疗。

公开(公告)号：US20050222172A1

公开(公告)日：2005-10-06

申请号：US10504677

申请日：2003-02-26

申请人： Alistair Lochead ,  Alain Nedelec ,  Mourad Saady ,  Philippe Yaiche

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

IPC分类号： A61K31/519 ,  A61P3/04 ,  A61P3/10 ,  A61P9/10 ,  A61P17/14 ,  A61P21/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/08 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P27/02 ,  A61P27/06 ,  A61P35/00 ,  A61P43/00 ,  C07D487/04 ,  C07D519/00

CPC分类号： A61K31/519 ,  A01N43/90 ,  C07D487/04

摘要： The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: (1) 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.

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：（1）X表示两个氢原子，硫原子，氧原子或C 1-12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2,3或4-吡啶环或任选取代的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式（II）的杂环双环，R 3表示氢原子，C 1 -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变性疾病，例如阿尔茨海默病 。

公开(公告)号：US20050119280A1

公开(公告)日：2005-06-02

申请号：US10504679

申请日：2003-02-26

申请人： Alistair Lochead ,  Mourad Saady ,  Philippe Yaiche

发明人： Alistair Lochead ,  Mourad Saady ,  Philippe Yaiche

IPC分类号： A61K31/437 ,  A61K31/519 ,  A61P3/04 ,  A61P3/10 ,  A61P9/10 ,  A61P17/14 ,  A61P25/02 ,  A61P25/08 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P27/06 ,  A61P35/00 ,  C07D487/04

CPC分类号： C07D487/04

摘要： The invention relates to a imidazo[1,2-a]pyrimidone derivative represented by formula (I) or a salt thereof: R1 wherein X represents a bond, an ethenylene group, an ethenylene group, a methylene group optionally substituted; a carbonyl group, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide group or a nitrogen atom being optionally substituted; R1 represents a 2, 4 or 5-pyrimidinyl optionally substituted; R2 represents a C1-6 alkyl group, a C1-2 perhalogenated alkyl group,a C1-3 halogenated alkyl group, a benzyl group, a benzene ring, a naphthalene ring, 5,6,7,8-tetrahydronaphthalene ring, a pyridine 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; 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, such as Alzheimer disease.

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：R 1其中X表示键，亚乙烯基，亚乙烯基， 任选取代的亚甲基; 羰基，氧原子，硫原子，磺酰基，亚砜基或任选取代的氮原子; R 1表示任选取代的2,4或5-嘧啶基; R 2表示C 1-6烷基，C 1-12全卤代烷基，C 1-3烷基， 卤代烷基，苄基，苯环，萘环，5,6,7,8-四氢萘环，吡啶环，吲哚环，吡咯环，噻吩环，呋喃环或呋喃环 咪唑环，苄基和环任选被取代; 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GSK3beta异常活动引起的神经变性疾病，例如阿尔茨海默氏症 疾病。