公开(公告)号：US08252810B2

公开(公告)日：2012-08-28

申请号：US12368069

申请日：2009-02-09

申请人： Fumihiro Ozaki ,  Motohiro Soejima ,  Tasuku Ishida ,  Yoshihiko Norimine ,  Nobuyuki Kurusu ,  Eriko Doi ,  Toshihiko Kaneko ,  Daiju Hasegawa ,  Kiyoaki Kobayashi ,  Noboru Yamamoto

发明人： Fumihiro Ozaki ,  Motohiro Soejima ,  Tasuku Ishida ,  Yoshihiko Norimine ,  Nobuyuki Kurusu ,  Eriko Doi ,  Toshihiko Kaneko ,  Daiju Hasegawa ,  Kiyoaki Kobayashi ,  Noboru Yamamoto

IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D221/02

CPC分类号： C07D451/06 ,  C07D451/02 ,  C07D451/04 ,  C07D519/00

摘要： Compounds represented by formula (I) and pharmaceutically acceptable salts thereof have excellent sodium channel inhibitory action and are useful as therapeutic agents and analgesics for various kinds of neuralgia, neuropathy, epilepsy, insomnia, premature ejaculation and the like. wherein Q represents ethylene, etc., R1, R2 and R3 represent hydrogen, etc., X1 represents C1-6 alkylene, etc., X2 represents C1-6 alkylene, etc., A1 represents a 5- to 6-membered heterocyclic group, etc., and A2 represents C6-14 aryl, etc.

摘要翻译： 由式（I）表示的化合物及其药学上可接受的盐具有优异的钠通道抑制作用，可用作各种神经痛，神经病，癫痫，失眠，早泄等的治疗剂和止痛剂。 其中Q表示亚乙基等，R 1，R 2和R 3表示氢等，X 1表示C 1-6亚烷基等，X 2表示C 1-6亚烷基等，A 1表示5〜6元杂环基 等，A2代表C6-14芳基等。

公开(公告)号：US08158620B2

公开(公告)日：2012-04-17

申请号：US12355154

申请日：2009-01-16

申请人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Kunitoshi Takeda ,  Yoichi Kita ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

发明人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Kunitoshi Takeda ,  Yoichi Kita ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

IPC分类号： C07D513/02 ,  C07D279/08 ,  A61K31/542

CPC分类号： A61K31/542 ,  C07D279/08 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04

摘要： A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is —NReCO— or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 由通式表示的化合物或其药学上可接受的盐或其溶剂化物，其中环A是C 6-14芳基等，L是-NReCO-等（其中Re是氢原子或 环）B是C 6-14芳基等，X是C 1-3亚烷基等，Y是单键等，Z是C 1-3亚烷基等，R 1 和R 2各自独立地为氢原子等，R 3，R 4，R 5和R 6独立地为氢原子，卤素原子等，具有A＆bgr; 产生抑制作用或BACE1抑制作用，可用作由A＆Bgr引起的神经变性疾病的预防或治疗剂; 并以阿尔茨海默氏型痴呆为代表。

公开(公告)号：US20120094984A1

公开(公告)日：2012-04-19

申请号：US13333238

申请日：2011-12-21

申请人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Kunitoshi Takeda ,  Yoichi Kita ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

发明人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Kunitoshi Takeda ,  Yoichi Kita ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

IPC分类号： A61K31/5415 ,  A61P25/28 ,  C07D279/08 ,  C07D471/04 ,  C07D417/12 ,  C07D513/04

CPC分类号： A61K31/542 ,  C07D279/08 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04

摘要： A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is —NReCO— or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 由通式表示的化合物或其药学上可接受的盐或其溶剂化物，其中环A是C 6-14芳基等，L是-NReCO-等（其中Re是氢原子或 环）B是C 6-14芳基等，X是C 1-3亚烷基等，Y是单键等，Z是C 1-3亚烷基等，R 1 和R 2各自独立地为氢原子等，R 3，R 4，R 5和R 6独立地为氢原子，卤素原子等，具有A＆bgr; 产生抑制作用或BACE1抑制作用，可用作由A＆Bgr引起的神经变性疾病的预防或治疗剂; 并以阿尔茨海默氏型痴呆为代表。

公开(公告)号：US20100317850A1

公开(公告)日：2010-12-16

申请号：US12863364

申请日：2009-01-16

申请人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Kunitoshi Takeda ,  Yoichi Kita ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

发明人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Kunitoshi Takeda ,  Yoichi Kita ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

IPC分类号： C07D513/04 ,  C07D417/12

CPC分类号： A61K31/542 ,  C07D279/08 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04

摘要： Disclosed is a compound represented by General formula (I), a pharmaceutically acceptable salt thereof, or a solvate of the compound or the pharmaceutically acceptable salt, which has an inhibitory activity of the production of Aβ or a BACE1-inhibiting activity, and is therefore useful as a prophylactic or therapeutic agent for Aβ-induced neurodegenerative diseases typified by Alzheimer-type dementia. Wherein the ring A represents a C6-14 aryl group or the like; L represents —NReCO— [wherein Re represents a hydrogen atom or the like] or the like; the ring B represents a C6-14 aryl group or the like; X represents a C1-3 alkylene group or the like; Y represents a single bond or the like; Z represents a C1-3 alkylene group or the like; R1 and R2 independently represent a hydrogen atom or the like; and R3, R4, R5 and R6 independently represent a hydrogen atom, a halogen atom or the like.

摘要翻译： 公开了通式（I）表示的化合物或其药学上可接受的盐，或该化合物或其药学上可接受的盐的溶剂化物，其具有抑制A＆Bgr生产的活性; 或BACE1抑制活性，因此可用作用于以阿尔茨海默氏型痴呆为代表的引起神经退行性疾病的预防或治疗剂。 其中环A表示C6-14芳基等; L表示-NReCO- [其中Re表示氢原子等]等; 环B表示C 6-14芳基等; X表示C1-3亚烷基等; Y表示单键等; Z表示C1-3亚烷基等; R1和R2独立地表示氢原子等; R 3，R 4，R 5和R 6独立地表示氢原子，卤素原子等。

公开(公告)号：US20090209755A1

公开(公告)日：2009-08-20

申请号：US12355154

申请日：2009-01-16

申请人： Yuichi SUZUKI ,  Takafumi MOTOKI ,  Toshihiko KANEKO ,  Mamoru TAKAISHI ,  Tasuku ISHIDA ,  Yoichi KITA ,  Kunitoshi TAKEDA ,  Noboru YAMAMOTO ,  Afzal KHAN ,  Paschalis DIMOPOULOS

发明人： Yuichi SUZUKI ,  Takafumi MOTOKI ,  Toshihiko KANEKO ,  Mamoru TAKAISHI ,  Tasuku ISHIDA ,  Yoichi KITA ,  Kunitoshi TAKEDA ,  Noboru YAMAMOTO ,  Afzal KHAN ,  Paschalis DIMOPOULOS

IPC分类号： C07D513/02 ,  C07D279/08

CPC分类号： A61K31/542 ,  C07D279/08 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04

摘要： A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is —NReCO— or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 由通式表示的化合物或其药学上可接受的盐或其溶剂化物，其中环A是C 6-14芳基等，L是-NReCO-等（其中Re是氢原子或 环）B是C 6-14芳基等，X是C 1-3亚烷基等，Y是单键等，Z是C 1-3亚烷基等，R 1 和R 2各自独立地为氢原子等，R 3，R 4，R 5和R 6独立地为氢原子，卤素原子等，具有Aβ生产抑制作用或BACE1抑制作用，可用作预防性 或由Abeta引起并以阿尔茨海默氏型痴呆为代表的神经变性疾病的治疗剂。

公开(公告)号：US09175013B2

公开(公告)日：2015-11-03

申请号：US13979961

申请日：2012-01-19

申请人： Mamoru Takaishi ,  Tasuku Ishida

发明人： Mamoru Takaishi ,  Tasuku Ishida

IPC分类号： C07D513/04 ,  A61K31/542 ,  A61K45/06

CPC分类号： C07D513/04 ,  A61K31/542 ,  A61K45/06

摘要： The present invention relates to a fused aminodihydrothiazine derivative of formula (I): wherein X is hydrogen or fluorine; R is monofluoromethyl or difluoromethyl; and pharmaceutically acceptable salts thereof; which compound has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 本发明涉及式（I）的稠合氨基二氢噻嗪衍生物：其中X是氢或氟; R是单氟甲基或二氟甲基; 及其药学上可接受的盐; 该化合物具有A＆bgr; 产生抑制作用或BACE1抑制作用，可用作由A＆Bgr引起的神经变性疾病的预防或治疗剂; 并以阿尔茨海默氏型痴呆为代表。

公开(公告)号：US20140179690A1

公开(公告)日：2014-06-26

申请号：US13979961

申请日：2012-01-19

申请人： Mamoru Takaishi ,  Tasuku Ishida

发明人： Mamoru Takaishi ,  Tasuku Ishida

IPC分类号： C07D513/04 ,  A61K45/06 ,  A61K31/542

CPC分类号： C07D513/04 ,  A61K31/542 ,  A61K45/06

摘要： The present invention relates to a fused aminodihydrothiazine derivative of formula (I): wherein X is hydrogen or fluorine; R is monofluoromethyl or difluoromethyl; and pharmaceutically acceptable salts thereof; which compound has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 本发明涉及式（I）的稠合氨基二氢噻嗪衍生物：其中X是氢或氟; R是单氟甲基或二氟甲基; 及其药学上可接受的盐; 该化合物具有A＆bgr; 产生抑制作用或BACE1抑制作用，可用作由A＆Bgr引起的神经变性疾病的预防或治疗剂; 并以阿尔茨海默氏型痴呆为代表。

公开(公告)号：US20100331310A1

公开(公告)日：2010-12-30

申请号：US12867024

申请日：2009-02-09

申请人： Fumihiro Ozaki ,  Motohiro Soejima ,  Tasuku Ishida ,  Yoshihiko Norimine ,  Nobuyuki Kurusu ,  Eriko Doi ,  Toshihiko Kaneko ,  Daiju Hasegawa ,  Kiyoaki Kobayashi ,  Noboru Yamamoto

发明人： Fumihiro Ozaki ,  Motohiro Soejima ,  Tasuku Ishida ,  Yoshihiko Norimine ,  Nobuyuki Kurusu ,  Eriko Doi ,  Toshihiko Kaneko ,  Daiju Hasegawa ,  Kiyoaki Kobayashi ,  Noboru Yamamoto

IPC分类号： C07D451/02 ,  A61K31/517 ,  A61K31/535 ,  C07D498/02 ,  C07D513/02 ,  A61K31/4985 ,  A61P25/08 ,  A61K31/501 ,  A61P25/00 ,  A61K31/46 ,  A61K31/506 ,  A61K31/55 ,  A61K31/53 ,  A61K31/498 ,  A61K31/5365 ,  A61P15/00 ,  A61P3/10 ,  A61K31/495 ,  A61K31/5377

CPC分类号： C07D451/06 ,  C07D451/02 ,  C07D451/04 ,  C07D519/00

摘要： Compounds represented by formula (I) and pharmaceutically acceptable salts thereof have excellent sodium channel inhibitory action and are useful as therapeutic agents and analgesics for various kinds of neuralgia, neuropathy, epilepsy, insomnia, premature ejaculation and the like. wherein Q represents ethylene, etc., R1, R2 and R3 represent hydrogen, etc., X1 represents C1-6 alkylene, etc., X2 represents C1-6 alkylene, etc., A1 represents a 5- to 6-membered heterocyclic group, etc., and A2 represents C6-14 aryl, etc.

摘要翻译： 由式（I）表示的化合物及其药学上可接受的盐具有优异的钠通道抑制作用，可用作各种神经痛，神经病，癫痫，失眠，早泄等的治疗剂和止痛剂。 其中Q表示亚乙基等，R 1，R 2和R 3表示氢等，X 1表示C 1-6亚烷基等，X 2表示C 1-6亚烷基等，A 1表示5〜6元杂环基 等，A2代表C6-14芳基等。

公开(公告)号：US20100093999A1

公开(公告)日：2010-04-15

申请号：US12568151

申请日：2009-09-28

申请人： Takafumi Motoki ,  Kunitoshi Takeda ,  Yoichi Kita ,  Mamoru Takaishi ,  Yuichi Suzuki ,  Tasuku Ishida

发明人： Takafumi Motoki ,  Kunitoshi Takeda ,  Yoichi Kita ,  Mamoru Takaishi ,  Yuichi Suzuki ,  Tasuku Ishida

IPC分类号： C07D498/04

CPC分类号： C07D513/04

摘要： A compound represented by the general formula: wherein Ring A is a C6-14 aryl group or the like, L is —NRLCO— or the like (wherein RL is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a C1-3 alkylene group or the like, Z is an oxygen atom or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, or a pharmaceutically acceptable salt thereof, or a solvate thereof, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 由通式表示的化合物：其中环A是C 6-14芳基等，L是-NRLCO-等（其中RL是氢原子等），环B是C 6-14芳基 基团等，X是C 1-3亚烷基等，Y是C 1-3亚烷基等，Z是氧原子等，R 1和R 2各自独立地是氢原子等 ，R 3，R 4，R 5和R 6独立地为氢原子，卤素原子等或其药学上可接受的盐或其溶剂合物，具有A＆bgr; 产生抑制作用或BACE1抑制作用，可用作由A＆Bgr引起的神经变性疾病的治疗剂; 并以阿尔茨海默氏型痴呆为代表。

公开(公告)号：US08946210B2

公开(公告)日：2015-02-03

申请号：US13333238

申请日：2011-12-21

申请人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Yoichi Kita ,  Kunitoshi Takeda ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

发明人： Yuichi Suzuki ,  Takafumi Motoki ,  Toshihiko Kaneko ,  Mamoru Takaishi ,  Tasuku Ishida ,  Yoichi Kita ,  Kunitoshi Takeda ,  Noboru Yamamoto ,  Afzal Khan ,  Paschalis Dimopoulos

IPC分类号： C07D239/14 ,  A61K31/5415

CPC分类号： A61K31/542 ,  C07D279/08 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04

摘要： A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is —NReCO— or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

摘要翻译： 由通式表示的化合物或其药学上可接受的盐或其溶剂化物，其中环A是C 6-14芳基等，L是-NReCO-等（其中Re是氢原子或 环）B是C 6-14芳基等，X是C 1-3亚烷基等，Y是单键等，Z是C 1-3亚烷基等，R 1 和R 2各自独立地为氢原子等，R 3，R 4，R 5和R 6独立地为氢原子，卤素原子等，具有A＆bgr; 产生抑制作用或BACE1抑制作用，可用作由A＆Bgr引起的神经变性疾病的预防或治疗剂; 并以阿尔茨海默氏型痴呆为代表。