公开(公告)号：US08598175B2

公开(公告)日：2013-12-03

申请号：US12606669

申请日：2009-10-27

申请人： Nathalie Chereze ,  Thierry Gallet ,  Alistair Lochead ,  Mourad Saady ,  Corinne Veronique ,  Philippe Yaiche

发明人： Nathalie Chereze ,  Thierry Gallet ,  Alistair Lochead ,  Mourad Saady ,  Corinne Veronique ,  Philippe Yaiche

IPC分类号： C07D403/14 ,  C07D239/38 ,  A61K31/495

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

摘要： The present invention discloses a series of pyrimidone derivatives represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: Wherein X, Z, R1, R2, R3, R4, R5, R6, R7, n and m are as defined herein. Also disclosed herein are the methods of preparation of compounds of formula (I), intermediates therefor and their utility in treating a variety of disease conditions.

摘要翻译： 本发明公开了一系列由式（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，Z，R1，R2，R3，R4，R5，R6，R7，n和 m如本文所定义。 本文还公开了制备式（I）化合物，其中间体及其在治疗各种疾病状况中的用途的方法。

公开(公告)号：US08592436B2

公开(公告)日：2013-11-26

申请号：US12606656

申请日：2009-10-27

申请人： Nathalie Chereze ,  Thierry Gallet ,  Alistair Lochead ,  Mourad Saady ,  Corinne Veronique ,  Philippe Yaiche

发明人： Nathalie Chereze ,  Thierry Gallet ,  Alistair Lochead ,  Mourad Saady ,  Corinne Veronique ,  Philippe Yaiche

IPC分类号： C07D239/36 ,  A61K31/513

CPC分类号： C07D239/36

摘要： The present invention discloses a series of pyrimidone derivatives represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: Wherein X, Z, R1, R2, R3, R4, R5, R6, R7, n and m are as defined herein. Also disclosed herein are the methods of preparation of compounds of formula (I), intermediates therefor and their utility in treating a variety of disease conditions.

摘要翻译： 本发明公开了一系列由式（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，Z，R1，R2，R3，R4，R5，R6，R7，n和 m如本文所定义。 本文还公开了制备式（I）化合物，其中间体及其在治疗各种疾病状况中的用途的方法。

公开(公告)号：US20110319381A1

公开(公告)日：2011-12-29

申请号：US13145926

申请日：2010-02-04

申请人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

发明人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

IPC分类号： A61K31/4439 ,  C07D413/14 ,  A61K31/4709 ,  A61K31/444 ,  A61K31/506 ,  A61K31/497 ,  A61P29/00 ,  A61P1/08 ,  A61P25/00 ,  A61P25/28 ,  A61P37/00 ,  A61P1/00 ,  A61P35/00 ,  A61P31/00 ,  A61P33/00 ,  A61P9/10 ,  C07D417/14

CPC分类号： C07D417/14 ,  C07D413/14

摘要： The invention relates to a compound of the general formula (I) in which R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy, NR8R9 group; m, n, o and p are independently an integer equal to 0, 1, 2 or 3; A is a covalent bond or a C1-8-alkylene group; R1 is an optionally substituted aryl or heteroaryl group; R3 is a hydrogen or fluorine atom or a C1-6-alkyl group or a trifluoromethyl group; R4 is an optionally substituted 5-member heterocyclic compound; the compound being in the form of a base or acid addition salt. The invention also relates to the therapeutic use thereof.

摘要翻译： 本发明涉及其中R 2为氢或氟原子或羟基，氰基，三氟甲基，C 1-6 - 烷基，C 1-6 - 烷氧基，NR 8 R 9基团的通式（I）的化合物; m，n，o和p独立地为等于0,1,2或3的整数; A是共价键或C 1-8亚烷基; R1是任选取代的芳基或杂芳基; R3是氢或氟原子或C1-6烷基或三氟甲基; R4是任选取代的5元杂环化合物; 该化合物为碱或酸加成盐的形式。 本发明还涉及其治疗用途。

公开(公告)号：US08148364B2

公开(公告)日：2012-04-03

申请号：US12122111

申请日：2008-05-16

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： C07D239/00 ,  C07D223/00 ,  A61K31/55 ,  A61K31/519 ,  A61P25/28

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, Z, R1, R2, R3, R4, R5, R6, R7, n, m, and o 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： 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，Z，R1，R2，R3，R4，R5，R6，R7，n，m和o分别为 在此描述。 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，其用于预防和/或治疗由GSK3和bgr的异常活性如阿尔茨海默病引起的神经退行性疾病。

公开(公告)号：US07547705B2

公开(公告)日：2009-06-16

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： A61K31/397 ,  A61K31/551 ,  A61K31/527 ,  A61K31/4162 ,  C07D225/00 ,  C07D223/00 ,  C07D487/20 ,  C07D239/00 ,  A61P3/10 ,  A61P25/28 ,  A61P25/16 ,  A61P25/18

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, Y, R1, R2, R3, R4, o, m, 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 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，Y，R1，R2，R3，R4，o，m，n，p和q如上所定义 这里。 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：US08394787B2

公开(公告)日：2013-03-12

申请号：US13320199

申请日：2010-05-11

申请人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

发明人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

IPC分类号： A61K31/397 ,  C07D205/12 ,  C07D263/30 ,  C07D261/06 ,  C07D221/20 ,  A61K31/422 ,  A61K31/421 ,  A61K31/438

CPC分类号： C07D263/32 ,  C07D209/54 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12

摘要： The invention relates to compounds of the general formula (I) where: R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy, or NR8R9 group; m, n, o and p independently are a number from 0 to 3, provided that m+n≦7 and that o+p≦7; A is a covalent bond, an oxygen atom, a C1-6-alkylene group or a —O—C1-6-alkylene group in which the end that is an oxygen atom is bonded to the R1 group and the end that is an alkylene group is bonded to the carbon of the bicyclic compound; R1 is an optionally substituted aryl or heteroaryl group; R3 is a hydrogen or fluorine atom or a C1-6-alkyl or trifluoromethyl group; R4 is an optionally substituted 5-membered heterocyclic compounds; wherein the compounds can be in the state of a base or an acid addition salt. The invention can be used in therapeutics.

摘要翻译： 本发明涉及通式（I）的化合物，其中：R 2是氢或氟原子，或羟基，氰基，三氟甲基，C 1-6 - 烷基，C 1-6 - 烷氧基或NR 8 R 9基团; m，n，o和p独立地为0至3的数，条件是2＆nlE; m + n＆nlE; 5和2＆nlE; o + p＆nlE; 5; A是共价键，氧原子，C 1-6 - 亚烷基或-O-C 1-6 - 亚烷基，其中作为氧原子的末端键合到R 1基团，末端是亚烷基 基团与双环化合物的碳键合; R1是任选取代的芳基或杂芳基; R3是氢或氟原子或C1-6烷基或三氟甲基; R4是任选取代的5元杂环化合物; 其中所述化合物可以是碱或酸加成盐的状态。 本发明可用于治疗。

公开(公告)号：US20120129830A1

公开(公告)日：2012-05-24

申请号：US13320199

申请日：2010-05-11

申请人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

发明人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

IPC分类号： A61K31/438 ,  C07D263/40 ,  C07D401/12 ,  C07D413/12 ,  A61K31/422 ,  A61P29/00 ,  A61P25/00 ,  A61P1/08 ,  A61P25/28 ,  A61P25/08 ,  A61P9/00 ,  A61P35/00 ,  A61P13/12 ,  A61P37/02 ,  A61P37/08 ,  A61P33/00 ,  A61P31/12 ,  A61P31/04 ,  A61P19/08 ,  A61P27/02 ,  A61P1/00 ,  A61P13/02 ,  C07D417/12

CPC分类号： C07D263/32 ,  C07D209/54 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12

摘要： The invention relates to compounds of the general formula (I) where: R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy, or NR8R9 group; m, n, o and p independently are a number from 0 to 3, provided that m+n≦7 and that o+p≦7; A is a covalent bond, an oxygen atom, a C1-6-alkylene group or a —O—C1-6-alkylene group in which the end that is an oxygen atom is bonded to the R1 group and the end that is an alkylene group is bonded to the carbon of the bicyclic compound; R1 is an optionally substituted aryl or heteroaryl group; R3 is a hydrogen or fluorine atom or a C1-6-alkyl or trifluoromethyl group; R4 is an optionally substituted 5-membered heterocyclic compounds; wherein the compounds can be in the state of a base or an acid addition salt. The invention can be used in therapeutics.

摘要翻译： 本发明涉及通式（I）的化合物，其中：R 2是氢或氟原子，或羟基，氰基，三氟甲基，C 1-6 - 烷基，C 1-6 - 烷氧基或NR 8 R 9基团; m，n，o和p独立地为0至3的数，条件是m + n＆nlE; 7和o + p＆nlE; 7; A是共价键，氧原子，C 1-6 - 亚烷基或-O-C 1-6 - 亚烷基，其中作为氧原子的末端键合到R 1基团，末端是亚烷基 基团与双环化合物的碳键合; R1是任选取代的芳基或杂芳基; R3是氢或氟原子或C1-6烷基或三氟甲基; R4是任选取代的5元杂环化合物; 其中所述化合物可以是碱或酸加成盐的状态。 本发明可用于治疗。

公开(公告)号：US20120015950A1

公开(公告)日：2012-01-19

申请号：US13129235

申请日：2009-11-13

申请人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Mourad Saady ,  Julien Vache ,  Corinne Veronique ,  Philippe Yaiche

发明人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Mourad Saady ,  Julien Vache ,  Corinne Veronique ,  Philippe Yaiche

IPC分类号： A61K31/498 ,  C07D413/14 ,  C07D241/36 ,  C07D237/30 ,  C07D401/14 ,  A61K31/4709 ,  A61K31/444 ,  A61K31/502 ,  A61K31/506 ,  A61P1/08 ,  A61P1/00 ,  A61P31/04 ,  A61P31/12 ,  A61P25/00 ,  A61P25/08 ,  A61P13/12 ,  A61P9/10 ,  A61P35/00 ,  C07D215/38

CPC分类号： C07D417/14 ,  C07D401/14 ,  C07D403/14 ,  C07D407/14 ,  C07D413/12 ,  C07D413/14

摘要： Compound corresponding to general formula (I): in which R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy or NR8R9 group; n is an integer equal to 1, 2 or 3 and m is an integer equal to 1 or 2; A is a covalent bond or a C1-8-alkylene group; R1 is a phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, naphthyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, cinnolinyl or naphthyridinyl group, this group being optionally substituted; R3 is a hydrogen or fluorine atom, a C1-6-alkyl group or a tritluoromethyl group; R4 is a group selected from furanyl, pyrrolyl, thienyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, imidazole, triazolyl, tetrazolyl, oxazolone, oxazolidinone, isoxazolone, isoxazolidinone, isothiazolone, isothiazolidinone, imidazolone, imidazolidinone, pyrazolone, pyrazolidinone, oxadiazolone, thiadiazolone and triazolone, this group being optionally substituted; in the form of a base or of an addition salt with an acid. Therapeutic use.

摘要翻译： 对应于通式（I）的化合物：其中R 2为氢或氟原子或羟基，氰基，三氟甲基，C 1-6 - 烷基，C 1-6 - 烷氧基或NR 8 R 9基团; n是等于1,2或3的整数，m是等于1或2的整数; A是共价键或C 1-8亚烷基; R 1是苯基，吡啶基，哒嗪基，嘧啶基，吡嗪基，三嗪基，萘基，喹啉基，异喹啉基，酞嗪基，喹唑啉基，喹喔啉基，噌啉基或萘啶基， R3是氢或氟原子，C1-6烷基或三氟甲基; R4是选自呋喃基，吡咯基，噻吩基，异噻唑基，恶唑基，异恶唑基，吡唑基，恶二唑基，噻二唑基，咪唑，三唑基，四唑基，恶唑酮，恶唑烷酮，异恶唑酮，异恶唑烷酮，异噻唑酮，异噻唑烷酮，咪唑啉酮，咪唑烷酮，吡唑啉酮，吡唑烷酮， 恶二唑酮，噻二唑酮和三唑酮，该基团任选被取代; 以碱的形式或与酸的加成盐形式。 治疗用途。

公开(公告)号：US08889702B2

公开(公告)日：2014-11-18

申请号：US13145926

申请日：2010-02-04

申请人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

发明人： Ahmed Abouabdellah ,  Nathalie Chereze ,  Aude Fayol ,  Alistair Lochead ,  Mourad Saady ,  Julien Vache ,  Philippe Yaiche

IPC分类号： A61K31/4704 ,  A61K31/4427 ,  C07D413/14 ,  C07D417/14

CPC分类号： C07D417/14 ,  C07D413/14

摘要： The invention relates to a compound of the general formula (I) in which R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy, NR8R9 group; m, n, o and p are independently an integer equal to 0, 1, 2 or 3; A is a covalent bond or a C1-8-alkylene group; R1 is an optionally substituted aryl or heteroaryl group; R3 is a hydrogen or fluorine atom or a C1-6-alkyl group or a trifluoromethyl group; R4 is an optionally substituted 5-member heterocyclic compound; the compound being in the form of a base or acid addition salt. The invention also relates to the therapeutic use thereof.

摘要翻译： 本发明涉及其中R 2为氢或氟原子或羟基，氰基，三氟甲基，C 1-6 - 烷基，C 1-6 - 烷氧基，NR 8 R 9基团的通式（I）的化合物; m，n，o和p独立地为等于0,1,2或3的整数; A是共价键或C 1-8亚烷基; R1是任选取代的芳基或杂芳基; R3是氢或氟原子或C1-6烷基或三氟甲基; R4是任选取代的5元杂环化合物; 该化合物为碱或酸加成盐的形式。 本发明还涉及其治疗用途。

公开(公告)号：US07294631B2

公开(公告)日：2007-11-13

申请号：US11423557

申请日：2006-06-12

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 ,  A61K31/551 ,  C07D225/08 ,  C07D239/20 ,  C07D487/20 ,  C07D495/10

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, Y, R1, R2, R3, R4, o, m, 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 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，Y，R 1，R 2，R 3，R 4，o，m，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，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。