公开(公告)号：US20100256191A1

公开(公告)日：2010-10-07

申请号：US12744444

申请日：2008-12-26

Applicant: Takahisa Hanada ,  Shigeki Hibi ,  Kazuki Miyazaki

Inventor： Takahisa Hanada ,  Shigeki Hibi ,  Kazuki Miyazaki

IPC: A61K31/444 ,  A61K31/423 ,  A61P25/08

CPC classification number: A61K45/06 ,  A61K31/423 ,  A61K31/444 ,  A61K2300/00

Abstract: The invention provides methods for treating epilepsy by administering to patients therapeutically effective amounts of AMPA receptor antagonists in combination with zonisamide useful for treating epilepsy. The invention also provides pharmaceutical combinations, kits, and pharmaceutical compositions comprising therapeutically effective amounts of AMPA receptor antagonists, and optionally, zonisamide that are useful for treating epilepsy.

Abstract translation: 本发明提供了通过向患者施用治疗有效量的AMPA受体拮抗剂与用于治疗癫痫的唑尼沙胺组合来治疗癫痫的方法。 本发明还提供药物组合，试剂盒和药物组合物，其包含治疗有效量的AMPA受体拮抗剂和任选的可用于治疗癫痫的唑尼沙胺。

公开(公告)号：US20090181985A1

公开(公告)日：2009-07-16

申请号：US12397132

申请日：2009-03-03

Applicant: Shigeki Hibi ,  Yoshinori Takahashi ,  Yorihisa Hoshino ,  Koichi Kikuchi ,  Motohiro Soejima ,  Tatsuya Yoshiuchi ,  Kogyoku Shin ,  Matsuko Ono ,  Hisashi Shibata ,  Mitsuhiro Ino ,  Tetsuya Hirakawa

Inventor： Shigeki Hibi ,  Yoshinori Takahashi ,  Yorihisa Hoshino ,  Koichi Kikuchi ,  Motohiro Soejima ,  Tatsuya Yoshiuchi ,  Kogyoku Shin ,  Matsuko Ono ,  Hisashi Shibata ,  Mitsuhiro Ino ,  Tetsuya Hirakawa

IPC: A61K31/519 ,  C07D487/02 ,  A61P25/18 ,  A61P25/22

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula or a salt thereof. Wherein R1 denotes a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group and the like; R2 denotes a halogen atom, a cyano group, a nitro group, a C1-10 alkyl group, a C2-10 alkenyl group, C2-10 alkynyl group and the like; R3 denotes a C6-14 aromatic hydrocarbon cyclic group or a 5- to 14-membered aromatic heterocyclic group, each of which may have a substituent; and X, Y and X are independent of each other and each denotes N or CR4 (wherein R4 denotes a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally halogenated C1-6 alkyl group and the like) and, in this case, at least two of X, Y and Z denote CR4.

Abstract translation: 本发明提供具有优异的促肾上腺皮质激素释放因子受体拮抗活性的新型化合物。 也就是说，它提供由下式表示的化合物或其盐。 其中R1表示氢原子，C1-6烷基，C1-6烷氧基等; R2表示卤素原子，氰基，硝基，C1-10烷基，C2-10烯基，C2-10炔基等; R3表示可以具有取代基的C 6-14芳族烃环状基团或5〜14元芳香族杂环基团。 X，Y和X彼此独立地表示N或CR4（其中R4表示氢原子，卤素原子，氰基，硝基，任意卤代的C 1-6烷基等）和 在这种情况下，X，Y和Z中的至少两个表示CR 4。

公开(公告)号：US07176216B2

公开(公告)日：2007-02-13

申请号：US10689088

申请日：2003-10-21

Applicant: Shigeki Hibi ,  Yorihisa Hoshino ,  Koichi Kikuchi ,  Kogyoku Shin ,  Yoshinori Takahashi ,  Masae Fujisawa ,  Hisashi Shibata ,  Mitsuhiro Ino

Inventor： Shigeki Hibi ,  Yorihisa Hoshino ,  Koichi Kikuchi ,  Kogyoku Shin ,  Yoshinori Takahashi ,  Masae Fujisawa ,  Hisashi Shibata ,  Mitsuhiro Ino

IPC: A61K31/44

CPC classification number: C07D471/04 ,  C07F5/025 ,  C07F7/1804

Abstract: A compound represented by the formula: [wherein R1 is methoxy, methylthio, ethyl, etc.; R5 and R6 are each independently cyclopropylmethyl, (4-tetrahydropyranyl)methyl, etc.; and two of R40, R41 and R42 are C1-6 alkoxy while the remaining one is methoxymethyl, etc.], a salt thereof, or a hydrate of the foregoing. This compound has excellent antagonism against corticotropin-releasing factor receptor.

Abstract translation: 由下式表示的化合物[其中R 1是甲氧基，甲硫基，乙基​​等; R 5和R 6各自独立地为环丙基甲基，（4-四氢吡喃基）甲基等; R 40，R 41和R 42中的两个是C 1-6烷氧基，而剩余的一个是 甲氧基甲基等]，其盐或上述的水合物。 该化合物对促肾上腺皮质激素释放因子受体具有优异的拮抗作用。

公开(公告)号：US07091215B2

公开(公告)日：2006-08-15

申请号：US10250693

申请日：2002-04-25

Applicant: Shigeki Hibi ,  Koichi Kikuchi ,  Yorihisa Hoshino ,  Motohiro Soejima ,  Tatsuya Yoshiuchi ,  Kogyoku Shin ,  Mutsuko Ono ,  Yoshinori Takahashi ,  Hisashi Shibata ,  Mitsuhiro Ino ,  Tetsuya Hirakawa

Inventor： Shigeki Hibi ,  Koichi Kikuchi ,  Yorihisa Hoshino ,  Motohiro Soejima ,  Tatsuya Yoshiuchi ,  Kogyoku Shin ,  Mutsuko Ono ,  Yoshinori Takahashi ,  Hisashi Shibata ,  Mitsuhiro Ino ,  Tetsuya Hirakawa

IPC: C07D471/02 ,  A61K31/437

CPC classification number: C07D471/04 ,  A61K31/437 ,  C07F5/025 ,  C07F7/2208

Abstract: Compounds represented by the general formula: [wherein R1 represents methoxy, ethyl, methylthio, etc., R2, R3 and R4 each represent hydrogen, a halogen, etc., R5 and R6 each represent —X5—X6—X7 (wherein X5 represents a single bond or —CO—, X6 represents a single bond, —NR3a, etc. and X7 and R3a each represent hydrogen, C1-10 alkyl, etc.), and Ar represents phenyl, pyridyl, etc.], salts thereof and hydrates of the foregoing.

Abstract translation: 由以下通式表示的化合物：其中R 1表示甲氧基，乙基，甲硫基等，R 2，R 3和R 3， SUP> 4 各自表示氢，卤素等，R 5和R 6各自表示-X 5〜 其中X 5表示单键或-CO-，X 6表示单键 键，-NR 3a等，X 7和R 9各自表示氢，C 1-10烷基， 烷基等），Ar表示苯基，吡啶基等]，其盐和上述的水合物。

公开(公告)号：US20050004159A1

公开(公告)日：2005-01-06

申请号：US10903387

申请日：2004-08-02

Applicant: Shigeki Hibi ,  Yorihisa Hoshino ,  Tatsuya Yoshiuchi ,  Kogyoku Shin ,  Kouichi Kikuchi ,  Motohiro Soejima ,  Mutsuko Tabata ,  Yoshinori Takahashi ,  Hisashi Shibata ,  Takayuki Hida ,  Tetsuya Hirakawa ,  Mitsuhiro Ino

Inventor： Shigeki Hibi ,  Yorihisa Hoshino ,  Tatsuya Yoshiuchi ,  Kogyoku Shin ,  Kouichi Kikuchi ,  Motohiro Soejima ,  Mutsuko Tabata ,  Yoshinori Takahashi ,  Hisashi Shibata ,  Takayuki Hida ,  Tetsuya Hirakawa ,  Mitsuhiro Ino

IPC: A61P1/04 ,  A61P1/08 ,  A61P1/10 ,  A61P1/12 ,  A61P1/14 ,  A61P9/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  C07D471/14 ,  C07D487/14 ,  C07D491/14 ,  A61K31/4745 ,  C07D471/02

CPC classification number: C07D471/14 ,  C07D487/14 ,  C07D491/14

Abstract: The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula, a pharmacologically acceptable salt thereof or hydrates thereof. Wherein A, B and D are the same as or different from each other and each represents a group represented by the formula —(CR1R2)m— (wherein R1 and R2 are the same as or different from each other and each represents a C1-6 alkyl group etc.), —NR3— (wherein R3 represetns hydrogen etc.) etc.; E and G are the same as or different from each other and each represents a group represented by the formula —(CR6R7)p— (wherein R6 and R7 are the same as or different from each other and each represents hydrogen etc.; and p represents an integer of 0, 1 or 2); J represents a carbon atom or nitrogen atom, each substituted with C1-6 alkyl group optionally substituted with a halogen atom, etc.; K and L are the same as or different from each other and each represents carbon atom or nitrogen atom; M means hydrogen, a halogen atom, an optionally substituted C1-6 alkyl group etc.; and the partial structure means a single or double bond.

Abstract translation: 本发明提供具有优异的促肾上腺皮质激素释放因子受体拮抗活性的新型化合物。 也就是说，它提供由下式表示的化合物，其药理学上可接受的盐或其水合物。 其中A，B和D彼此相同或不同，并且各自表示由式 - （CR 1 R 2）m - 表示的基团（其中R 1和R 2为 相同或不同，各自表示C1-6烷基等），-NR 3 - （其中R 3表示氢等）等; E和G彼此相同或不同，并且各自表示由下式表示的基团 - （CR 6 R 7）p - （其中R 6和R 7与 彼此不同，各自表示氢等; p表示0,1或2的整数）; J表示碳原子或氮原子，各自被任选被卤素原子取代的C 1-6烷基取代; K和L彼此相同或不同，各自表示碳原子或氮原子; M表示氢，卤原子，任意取代的C 1-6烷基等; 并且部分结构表示单键或双键。

公开(公告)号：US06541474B2

公开(公告)日：2003-04-01

申请号：US09910012

申请日：2001-07-23

Applicant: Kouichi Kikuchi ,  Katsuya Tagami ,  Hiroyuki Yoshimura ,  Shigeki Hibi ,  Mitsuo Nagai ,  Shinya Abe ,  Makoto Okita ,  Takayuki Hida ,  Seiko Higashi ,  Naoki Tokuhara ,  Seiichi Kobayashi

Inventor： Kouichi Kikuchi ,  Katsuya Tagami ,  Hiroyuki Yoshimura ,  Shigeki Hibi ,  Mitsuo Nagai ,  Shinya Abe ,  Makoto Okita ,  Takayuki Hida ,  Seiko Higashi ,  Naoki Tokuhara ,  Seiichi Kobayashi

IPC: A61K314965

CPC classification number: C07D401/04 ,  C07D209/14 ,  C07D231/12 ,  C07D241/24 ,  C07D241/44 ,  C07D249/10 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D407/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04

Abstract: Described is a heterocycle-containing carboxylic acid derivative represented by the following formula (I): wherein A represents, for example, a heteroaryl group which contains at least one nitrogen atom and may have a substituent, B represents, for example, a heteroarylene group, a —CONH— group or a group represented by the formula —CR6═CR7— in which R6 and R7 represents H, a lower alkyl group or the like, D represents an arylene group, a heteroarylene group or the like, n1 stands for 0 or 1, M represents, for example, a hydroxyl group or a lower alkoxy group; or a physiologically acceptable salt thereof. As a retinoic-related compound replacing retinoic acid, it permits the provision of a preventive and/or therapeutic for various diseases.

Abstract translation: 描述了由下式（I）表示的含杂环羧酸衍生物：其中A表示例如含有至少一个氮原子并且可以具有取代基的杂芳基，B表示例如亚杂芳基 -CONH-基或由式-CR 6 = CR 7 - 表示的基团，其中R 6和R 7表示H，低级烷基等，D表示亚芳基，亚杂芳基等，n1表示 0或1，M表示例如羟基或低级烷氧基; 或其生理上可接受的盐。 作为视黄酸相关化合物代替视黄酸，它允许为各种疾病提供预防和/或治疗。

公开(公告)号：US06329402B1

公开(公告)日：2001-12-11

申请号：US09313087

申请日：1999-05-17

Applicant: Kouichi Kikuchi ,  Katsuya Tagami ,  Hiroyuki Yoshimura ,  Shigeki Hibi ,  Mitsuo Nagai ,  Shinya Abe ,  Makoto Okita ,  Takayuki Hida ,  Seiko Higashi ,  Naoki Tokuhara ,  Seiichi Kobayashi

Inventor： Kouichi Kikuchi ,  Katsuya Tagami ,  Hiroyuki Yoshimura ,  Shigeki Hibi ,  Mitsuo Nagai ,  Shinya Abe ,  Makoto Okita ,  Takayuki Hida ,  Seiko Higashi ,  Naoki Tokuhara ,  Seiichi Kobayashi

IPC: A61K31415

CPC classification number: C07D401/04 ,  C07D209/14 ,  C07D231/12 ,  C07D241/24 ,  C07D241/44 ,  C07D249/10 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D407/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04

Abstract: Described is a heterocycle-containing carboxylic acid derivative represented by the following formula (I): wherein A represents, for example, a heteroaryl group which contains at least one nitrogen atom and may have a substituent, B represents, for example, a heteroarylene group, a —CONH— group or a group represented by the formula —CR6═CR7— in which R6 and R7 represents H, a lower alkyl group or the like, D represents an arylene group, a heteroarylene group or the like, n1 stands for 0 or 1, M represents, for example, a hydroxyl group or a lower alkoxy group; or a physiologically acceptable salt thereof. As a retinoic-related compound replacing retinoic acid, it permits the provision of a preventive and/or therapeutic for various diseases.

Abstract translation: 描述了由下式（I）表示的含杂环羧酸衍生物：其中A表示例如含有至少一个氮原子并且可以具有取代基的杂芳基，B表示例如亚杂芳基 -CONH-基或由式-CR 6 = CR 7 - 表示的基团，其中R 6和R 7表示H，低级烷基等，D表示亚芳基，亚杂芳基等，n1表示 0或1，M表示例如羟基或低级烷氧基; 或其生理上可接受的盐。 作为视黄酸相关化合物代替视黄酸，它允许为各种疾病提供预防和/或治疗。

公开(公告)号：US6133283A

公开(公告)日：2000-10-17

申请号：US236644

申请日：1999-01-26

Applicant: Shigeki Hibi ,  Kouichi Kikuchi ,  Hiroyuki Yoshimura ,  Mitsuo Nagai ,  Katsuya Tagami ,  Shinya Abe ,  Ieharu Hishinuma ,  Junichi Nagakawa ,  Norimasa Miyamoto ,  Takayuki Hida ,  Aichi Ogasawara ,  Seiko Higashi ,  Kenji Tai ,  Takashi Yamanaka ,  Makoto Asada

Inventor： Shigeki Hibi ,  Kouichi Kikuchi ,  Hiroyuki Yoshimura ,  Mitsuo Nagai ,  Katsuya Tagami ,  Shinya Abe ,  Ieharu Hishinuma ,  Junichi Nagakawa ,  Norimasa Miyamoto ,  Takayuki Hida ,  Aichi Ogasawara ,  Seiko Higashi ,  Kenji Tai ,  Takashi Yamanaka ,  Makoto Asada

IPC: A61P19/02 ,  C07C57/03 ,  C07C229/44 ,  C07D209/08 ,  C07D213/69 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D223/16 ,  C07D225/06 ,  C07D231/12 ,  C07D241/38 ,  C07D241/42 ,  C07D241/46 ,  C07D261/18 ,  C07D263/32 ,  C07D265/36 ,  C07D333/76 ,  C07D405/14 ,  C07D455/04 ,  C07D487/04 ,  C07D495/04 ,  G06F17/30 ,  C07D455/06 ,  A61K31/44

CPC classification number: C07D213/69 ,  C07C229/44 ,  C07C57/03 ,  C07D209/08 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D223/16 ,  C07D225/06 ,  C07D231/12 ,  C07D233/16 ,  C07D241/38 ,  C07D241/42 ,  C07D241/46 ,  C07D261/18 ,  C07D263/32 ,  C07D265/36 ,  C07D333/76 ,  C07D405/14 ,  C07D455/04 ,  C07D487/04 ,  C07D495/04 ,  G06F17/30607 ,  Y02P20/55

Abstract: To provide novel compounds relating to retinoid which can substitute for retinoic acid used for preventing and treating several diseases and having antagonism against retinoid. Heterocyclic compounds represented by the general formula (1-I) or physiologically acceptable salts thereof:Z--(CR.sup.3 .dbd.CR.sup.2).sub.n --COOR.sup.1-- (1-I)Compounds represented by the general formula (2-I) or physiologically acceptable salts thereof: ##STR1## The compounds according to the present invention exhibit extremely high ability to bind RARs and are effective for treating various kind of diseases such as abnormality in cornification and rheumatoid arthritis.

Abstract translation: 提供与维甲酸相关的新化合物，其可以代替用于预防和治疗几种疾病并对类视黄醇具有拮抗作用的视黄酸。 由通式（1-I）表示的杂环化合物或其生理学上可接受的盐：Z-（CR 3 = CR 2）n -COOR1-（1-I）由通式（2-I）表示的化合物或其生理学上可接受的盐 ：根据本发明的化合物显示出极高的结合RAR的能力，并且对于治疗各种类型的疾病如角质化和类风湿性关节炎的异常是有效的。

公开(公告)号：US6030964A

公开(公告)日：2000-02-29

申请号：US106112

申请日：1998-06-29

Applicant: Shigeki Hibi ,  Kouichi Kikuchi ,  Hiroyuki Yoshimura ,  Mitsuo Nagai ,  Katsuya Tagami ,  Shinya Abe ,  Ieharu Hishinuma ,  Junichi Nagakawa ,  Norimasa Miyamoto ,  Takayuki Hida ,  Aichi Ogasawara ,  Seiko Higashi ,  Kenji Tai ,  Takashi Yamanaka ,  Makoto Asada

Inventor： Shigeki Hibi ,  Kouichi Kikuchi ,  Hiroyuki Yoshimura ,  Mitsuo Nagai ,  Katsuya Tagami ,  Shinya Abe ,  Ieharu Hishinuma ,  Junichi Nagakawa ,  Norimasa Miyamoto ,  Takayuki Hida ,  Aichi Ogasawara ,  Seiko Higashi ,  Kenji Tai ,  Takashi Yamanaka ,  Makoto Asada

IPC: A61P19/02 ,  C07C57/03 ,  C07C229/44 ,  C07D209/08 ,  C07D213/69 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D223/16 ,  C07D225/06 ,  C07D231/12 ,  C07D241/38 ,  C07D241/42 ,  C07D241/46 ,  C07D261/18 ,  C07D263/32 ,  C07D265/36 ,  C07D333/76 ,  C07D405/14 ,  C07D455/04 ,  C07D487/04 ,  C07D495/04 ,  G06F17/30 ,  A61K31/55

CPC classification number: C07D213/69 ,  C07C229/44 ,  C07C57/03 ,  C07D209/08 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D223/16 ,  C07D225/06 ,  C07D231/12 ,  C07D233/16 ,  C07D241/38 ,  C07D241/42 ,  C07D241/46 ,  C07D261/18 ,  C07D263/32 ,  C07D265/36 ,  C07D333/76 ,  C07D405/14 ,  C07D455/04 ,  C07D487/04 ,  C07D495/04 ,  G06F17/30607 ,  Y02P20/55

Abstract: Compounds of the formula and compounds of the formula ##STR1## or their salts have the potent ability to bind to retinoic acid receptors thus useful in treating psoriasis and rheumatoid arthritis.

Abstract translation: 下式的化合物和下式化合物或其盐具有结合视黄酸受体的有效能力，因此可用于治疗牛皮癣和类风湿性关节炎。

公开(公告)号：US20100297181A1

公开(公告)日：2010-11-25

申请号：US12744454

申请日：2008-12-26

Applicant: Takahisa Hanada ,  Shigeki Hibi ,  Kazuki Miyazaki

Inventor： Takahisa Hanada ,  Shigeki Hibi ,  Kazuki Miyazaki

IPC: A61K31/444 ,  A61K31/496 ,  A61K39/08 ,  A61K31/55 ,  A61K31/5513 ,  A61K31/4985 ,  A61K31/675 ,  A61K31/53 ,  A61K31/542 ,  A61K31/57 ,  C07D213/22 ,  A61P25/08 ,  A61P25/22 ,  A61P25/18 ,  A61P27/16 ,  A61P27/06 ,  A61P25/24 ,  A61P9/10

CPC classification number: A61K45/06 ,  A61K31/4412 ,  A61K2300/00

Abstract: The invention provides methods for treating epilepsy, mental disorders and/or deficits in sensory organ by administering to patients therapeutically effective amounts of AMPA receptor antagonists in combination with one or more other active ingredients useful for treating epilepsy, mental disorders and/or deficits in sensory organ. The invention also provides pharmaceutical combinations, kits, and pharmaceutical compositions comprising therapeutically effective amounts of AMPA receptor antagonists, and optionally, one or more other active ingredients that are useful for treating epilepsy, mental disorders and/or deficits in sensory organ.

Abstract translation: 本发明提供了通过向患者施用治疗有效量的AMPA受体拮抗剂与用于治疗癫痫的一种或多种其它活性成分，精神障碍和/或感觉缺陷来治疗癫痫症，精神障碍和/或感觉器官缺陷的方法 器官。 本发明还提供药物组合，试剂盒和药物组合物，其包含治疗有效量的AMPA受体拮抗剂和任选的一种或多种可用于治疗感觉器官的癫痫，精神障碍和/或缺陷的其它活性成分。