公开(公告)号：US20060252768A1

公开(公告)日：2006-11-09

申请号：US10550299

申请日：2004-03-26

申请人： Kazutoshi Watanabe ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima ,  Yoshihiro Usui ,  Masahiro Okuyama ,  Aya Shoda ,  Keiichi Aritomo ,  Toshiyuki Kohara ,  Kenji Fukunaga

发明人： Kazutoshi Watanabe ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima ,  Yoshihiro Usui ,  Masahiro Okuyama ,  Aya Shoda ,  Keiichi Aritomo ,  Toshiyuki Kohara ,  Kenji Fukunaga

IPC分类号： A61K31/513 ,  C07D403/14

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C1-C12 alkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C1-C8 alkyl group, an optionally partially hydrogenated C6-C10 aryl ring, an indan ring or the like; m represents an integer of 1 to 3; each independently represents a halogen atom, a hydroxy group, a cyano group, a C1-C6 alkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C2-C6 alkylene group.

摘要翻译： 具有由式（I）表示的tau蛋白激酶1抑制活性的嘧啶酮衍生物或其盐或其溶剂合物或其水合物; 可用于疾病的预防和/或治疗性治疗，例如神经变性疾病（例如阿尔茨海默病）; 其中Q表示CH或氮原子; R表示C 1 -C 12烷基; 式（I）的环表示哌嗪环或哌啶环; 每个X独立地表示C 1 -C 8烷基，任选部分氢化的C 6 -C 10烷基， 芳环，茚满环等; m表示1〜3的整数， 各自独立地表示卤素原子，羟基，氰基，C 1 -C 6烷基等; n表示0〜8的整数， 当X和Y或两个Y基团连接在同一个碳原子上时，它们可以彼此结合形成C 2 -C 6亚烷基。

公开(公告)号：US07504411B2

公开(公告)日：2009-03-17

申请号：US10550299

申请日：2004-03-26

申请人： Kazutoshi Watanabe ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima ,  Yoshihiro Usui ,  Masahiro Okuyama ,  Aya Shoda ,  Keiichi Aritomo ,  Toshiyuki Kohara ,  Kenji Fukunaga

发明人： Kazutoshi Watanabe ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima ,  Yoshihiro Usui ,  Masahiro Okuyama ,  Aya Shoda ,  Keiichi Aritomo ,  Toshiyuki Kohara ,  Kenji Fukunaga

IPC分类号： C07D401/14 ,  C07D403/14 ,  A61K31/496 ,  A61K31/506 ,  A61P3/10 ,  A61P25/28

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C1-C12 alkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C1-C8 alkyl group, an optionally partially hydrogenated C6-C10 aryl ring, an indan ring or the like; m represents an integer of 1 to 3; each independently represents a halogen atom, a hydroxy group, a cyano group, a C1-C6 alkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C2-C6 alkylene group.

摘要翻译： 具有由式（I）表示的tau蛋白激酶1抑制活性的嘧啶酮衍生物或其盐或其溶剂合物或其水合物; 可用于疾病的预防和/或治疗性治疗，例如神经变性疾病（例如阿尔茨海默病）; 其中Q表示CH或氮原子; R代表C1-C12烷基; 式（I）的环表示哌嗪环或哌啶环; 每个X独立地表示C1-C8烷基，任选部分氢化的C 6 -C 10芳基环，茚满环等; m表示1〜3的整数， 各自独立地表示卤素原子，羟基，氰基，C1-C6烷基等; n表示0〜8的整数， 当X和Y或两个Y基团连接在同一个碳原子上时，它们可以彼此结合形成C 2 -C 6亚烷基。

公开(公告)号：US08129377B2

公开(公告)日：2012-03-06

申请号：US11576062

申请日：2005-09-29

申请人： Kazutoshi Watanabe ,  Kenji Fukunaga ,  Toshiyuki Kohara ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima

发明人： Kazutoshi Watanabe ,  Kenji Fukunaga ,  Toshiyuki Kohara ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima

IPC分类号： A61K31/535 ,  A61K31/505 ,  A01N43/54 ,  C07D413/00

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D413/14

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R1 represents a C1-C12 alkyl; R2 represents a hydrogen atom or the like; R3 represents a halogen or the like; q represents an integer of 1 to 7; R4 represents a halogen or the like; p represents 0 or an integer of 1 to 5; R5 represents a C6-C10 aryl, a heterocycle or the like; and X represents oxygen, NH, or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物，其光学活性异构体或其药学上可接受的盐：其中R1表示C1-C12烷基; R2表示氢原子等; R3表示卤素等; q表示1〜7的整数， R4表示卤素等; p表示0或1〜5的整数。 R5表示C6-C10芳基，杂环等; X代表氧，NH等，其用于预防和/或治疗由tau蛋白激酶1多动症如神经变性疾病（例如阿尔茨海默病）引起的疾病。

公开(公告)号：US08106045B2

公开(公告)日：2012-01-31

申请号：US11573476

申请日：2005-09-09

申请人： Kazutoshi Watanabe ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Toshiyuki Kohara ,  Kenji Fukunaga ,  Satoshi Yokoshima

发明人： Kazutoshi Watanabe ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Toshiyuki Kohara ,  Kenji Fukunaga ,  Satoshi Yokoshima

IPC分类号： A61K31/535 ,  A61K31/54 ,  C07D413/00 ,  C07D413/14

CPC分类号： C07D413/14

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein X represents CH or N; represents a C1-C12 alkyl; R2 represents a hydrogen atom, or the like; R′ represents a C1-C6 alkyl or the like; q represents 0 or an integer of 1 to 7; Y represents a C1-C6 alkyl or the like; p represents 0 or an integer of 1 to 5; R represents a 2,3-dihydroindolyl or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物，其光学活性异构体或其药学上可接受的盐：其中X表示CH或N; 表示C1-C12烷基; R2表示氢原子等; R'表示C1-C6烷基等; q表示0或1〜7的整数， Y表示C1-C6烷基等; p表示0或1〜5的整数。 R表示2,3-二氢吲哚基等，其用于预防和/或治疗由tau蛋白激酶1多动症如神经变性疾病（例如阿尔茨海默病）引起的疾病。

公开(公告)号：US20090239864A1

公开(公告)日：2009-09-24

申请号：US11576062

申请日：2005-09-29

申请人： Kazutoshi Watanabe ,  Kenji Fukunaga ,  Toshiyuki Kohara ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima

发明人： Kazutoshi Watanabe ,  Kenji Fukunaga ,  Toshiyuki Kohara ,  Fumiaki Uehara ,  Shinsuke Hiki ,  Satoshi Yokoshima

IPC分类号： A61K31/5377 ,  C07D413/14 ,  A61P25/28 ,  A61P27/06 ,  A61P25/16 ,  A61P3/10

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D413/14

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R1 represents a C1-C12 alkyl; R2 represents a hydrogen atom or the like; R3 represents a halogen or the like; q represents an integer of 1 to 7; R4 represents a halogen or the like; p represents 0 or an integer of 1 to 5; R5 represents a C6-C10 aryl, a heterocycle or the like; and X represents oxygen, NH, or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物，其光学活性异构体或其药学上可接受的盐：其中R1表示C1-C12烷基; R2表示氢原子等; R3表示卤素等; q表示1〜7的整数， R4表示卤素等; p表示0或1〜5的整数， R5表示C6-C10芳基，杂环等; X代表氧，NH等，其用于预防和/或治疗由tau蛋白激酶1多动症如神经变性疾病（例如阿尔茨海默病）引起的疾病。

公开(公告)号：US20090233918A1

公开(公告)日：2009-09-17

申请号：US12282396

申请日：2007-03-14

申请人： Kenji Fukunaga ,  Toshiyuki Kohara ,  Kazutoshi Watanabe ,  Yoshihiro Usui ,  Fumiaki Uehara ,  Satoshi Yokoshima ,  Daiki Sakai ,  Shin-ichi Kusaka ,  Kazuki Nakayama

发明人： Kenji Fukunaga ,  Toshiyuki Kohara ,  Kazutoshi Watanabe ,  Yoshihiro Usui ,  Fumiaki Uehara ,  Satoshi Yokoshima ,  Daiki Sakai ,  Shin-ichi Kusaka ,  Kazuki Nakayama

IPC分类号： A61K31/538 ,  C07D403/02 ,  A61K31/506 ,  A61P25/00 ,  A61P3/00

CPC分类号： C07D413/14 ,  C07D401/04 ,  C07D401/14 ,  C07D403/14 ,  C07D409/14 ,  C07D453/06 ,  C07D493/04

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R2 represents a hydrogen or the like; R3 represents methyl group or the like; R20 represents a halogen atom or the like; q represents an integer of 0 to 3; Z represent nitrogen atom, CH, or the like; R4 represents hydrogen or the like; R5 represents hydrogen or the like; R6 represents a substituted alkyloxy and the like; p represents an integer of 0 to 3; X represents bond, CH2, oxygen atom, NH, or the like; any one or more of R5 and R6, R5 and R4, R6 and R4, X and R5, X and R4, X and R6, and R6 and R6 may combine to each other to form a ring, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物或其光学活性异构体或其药学上可接受的盐：其中R2表示氢等; R3表示甲基等; R 20表示卤素原子等; q表示0〜3的整数， Z表示氮原子，CH等; R4表示氢等; R5表示氢等; R6表示取代的烷氧基等; p表示0〜3的整数， X表示键，CH2，氧原子，NH等; R 5和R 6，R 5和R 4，R 6和R 4，X和R 5，X和R 4，X和R 6以及R 6和R 6中的任何一个或多个可以彼此结合形成环，其用于预防和/ 或治疗由tau蛋白激酶1多动症如神经变性疾病（例如阿尔茨海默病）引起的疾病。

公开(公告)号：US08569294B2

公开(公告)日：2013-10-29

申请号：US12282396

申请日：2007-03-14

申请人： Kenji Fukunaga ,  Toshiyuki Kohara ,  Kazutoshi Watanabe ,  Yoshihiro Usui ,  Fumiaki Uehara ,  Satoshi Yokoshima ,  Daiki Sakai ,  Shin-ichi Kusaka ,  Kazuki Nakayama

发明人： Kenji Fukunaga ,  Toshiyuki Kohara ,  Kazutoshi Watanabe ,  Yoshihiro Usui ,  Fumiaki Uehara ,  Satoshi Yokoshima ,  Daiki Sakai ,  Shin-ichi Kusaka ,  Kazuki Nakayama

IPC分类号： A61K31/535

CPC分类号： C07D413/14 ,  C07D401/04 ,  C07D401/14 ,  C07D403/14 ,  C07D409/14 ,  C07D453/06 ,  C07D493/04

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein R2 represents a hydrogen or the like; R3 represents methyl group or the like; R20 represents a halogen atom or the like; q represents an integer of 0 to 3; Z represent nitrogen atom, CH, or the like; R4 represents hydrogen or the like; R5 represents hydrogen or the like; R6 represents a substituted alkyloxy and the like; p represents an integer of 0 to 3; X represents bond, CH2, oxygen atom, NH, or the like; any one or more of R5 and R6, R5 and R4, R6 and R4, X and R5, X and R4, X and R6, and R6 and R6 may combine to each other to form a ring, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物或其光学活性异构体或其药学上可接受的盐：其中R2表示氢等; R3表示甲基等; R 20表示卤素原子等; q表示0〜3的整数， Z表示氮原子，CH等; R4表示氢等; R5表示氢等; R6表示取代的烷氧基等; p表示0〜3的整数， X表示键，CH2，氧原子，NH等; R 5和R 6，R 5和R 4，R 6和R 4，X和R 5，X和R 4，X和R 6以及R 6和R 6中的任何一个或多个可以彼此结合形成环，其用于预防和/ 或治疗由tau蛋白激酶1多动症如神经变性疾病（例如阿尔茨海默病）引起的疾病。

公开(公告)号：US08592417B2

公开(公告)日：2013-11-26

申请号：US12518997

申请日：2007-12-26

申请人： Kazutoshi Watanabe ,  Toshiyuki Kohara ,  Kenji Fukunaga ,  Fumiaki Uehara

发明人： Kazutoshi Watanabe ,  Toshiyuki Kohara ,  Kenji Fukunaga ,  Fumiaki Uehara

IPC分类号： A61K31/535 ,  C07D413/14

CPC分类号： C07D413/14

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein each R1 represents hydrogen atom or the like; X represents oxygen atom or the like; A represents a C3-C7 cycloalkyl group, a C6-C10 aryl group or a heterocyclic group; R6 represents a halogen atom or the like; s represents 0 or an integer of 1 to 5; Q represents a pyridine ring which may be substituted or pyrimidine ring; and R2 represents hydrogen atom or the like, which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物或其光学活性异构体或其药学上可接受的盐：其中每个R 1表示氢原子等; X表示氧原子等; A表示C 3 -C 7环烷基，C 6 -C 10芳基或杂环基; R6表示卤素原子等; s表示0或1〜5的整数， Q表示可以被取代或嘧啶环的吡啶环; R2代表氢原子等，其用于预防和/或治疗由tau蛋白激酶1的异常活性引起的疾病，例如神经变性疾病（例如阿尔茨海默病）。

公开(公告)号：US20100113775A1

公开(公告)日：2010-05-06

申请号：US12518997

申请日：2007-12-26

申请人： Kazutoshi Watanabe ,  Toshiyuki Kohara ,  Kenji Fukunaga ,  Fumiaki Uehara

发明人： Kazutoshi Watanabe ,  Toshiyuki Kohara ,  Kenji Fukunaga ,  Fumiaki Uehara

IPC分类号： C07D413/14

CPC分类号： C07D413/14

摘要： A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein each R1 represents hydrogen atom or the like; X represents oxygen atom or the like; A represents a C3-C7 cycloalkyl group, a C6-C10 aryl group or a heterocyclic group; R6 represents a halogen atom or the like; s represents 0 or an integer of 1 to 5; Q represents a pyridine ring which may be substituted or pyrimidine ring; and R2 represents hydrogen atom or the like, which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物或其光学活性异构体或其药学上可接受的盐：其中每个R 1表示氢原子等; X表示氧原子等; A表示C 3 -C 7环烷基，C 6 -C 10芳基或杂环基; R6表示卤素原子等; s表示0或1〜5的整数， Q表示可以被取代或嘧啶环的吡啶环; R2代表氢原子等，其用于预防和/或治疗由tau蛋白激酶1的异常活性引起的疾病，例如神经变性疾病（例如阿尔茨海默病）。

公开(公告)号：US09006232B2

公开(公告)日：2015-04-14

申请号：US13389512

申请日：2010-08-11

申请人： Kazuki Nakayama ,  Daiki Sakai ,  Kazutoshi Watanabe ,  Toshiyuki Kohara ,  Keiichi Aritomo

发明人： Kazuki Nakayama ,  Daiki Sakai ,  Kazutoshi Watanabe ,  Toshiyuki Kohara ,  Keiichi Aritomo

IPC分类号： A61K31/5377 ,  A61K31/536 ,  A61K31/505 ,  A61K31/55 ,  C07D403/14 ,  C07D413/14 ,  C07D265/14 ,  C07D401/12 ,  C07D233/76 ,  C07D401/14 ,  C07D407/12 ,  C07D409/14

CPC分类号： C07D401/12 ,  C07D233/76 ,  C07D401/14 ,  C07D407/12 ,  C07D409/14 ,  C07D413/14

摘要： A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: wherein Z represents nitrogen atom or C—X; X represents hydrogen atom or fluorine atom; R1 is hydrogen atom or a C1-C3 alkyl group; L represents single bond or a C1-C6 alkylene group which may be substituted; Y represents single bond, sulfur atom, oxygen atom, NH, or the like; R2 represents hydrogen atom or a cyclic group which may be substituted, which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

摘要翻译： 由式（I）表示的化合物或其药学上可接受的盐：其中Z表示氮原子或C-X; X表示氢原子或氟原子; R1是氢原子或C1-C3烷基; L表示单键或可以被取代的C1-C6亚烷基; Y表示单键，硫原子，氧原子，NH等; R2代表氢原子或可被取代的环状基团，其用于预防和/或治疗由tau蛋白激酶1的异常活性如神经变性疾病（例如阿尔茨海默病）引起的疾病。