公开(公告)号：EP2266557A1

公开(公告)日：2010-12-29

申请号：EP09735250.4

申请日：2009-04-20

申请人： Toyama Chemical Co., Ltd.

发明人： AIKAWA, Yukihiko ,  SHIOZAWA, Shunichi

IPC分类号： A61K31/194 ,  A61K31/42 ,  A61K31/423 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/573 ,  A61K45/06 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00

CPC分类号： A61K45/06 ,  A61K31/194 ,  A61K31/42 ,  A61K31/423 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/573 ,  A61K2300/00

摘要： Disclosed are use of a benzophenone derivative represented by general formula (I) or a salt thereof and one or more immunosuppressing agents in combination, and a pharmaceutical composition containing the benzophenone derivative or a salt thereof and one or more immunosuppressing agents. The use and the composition are useful for treatment or prevention of autoimmune diseases and the like. (In the formula, R 1 represents an optionally substituted heterocyclic group, a substituted phenyl group or the like; Z represents an alkylene group or the like; R 2 represents a carboxyl group, which may be protected by an alkyl group, or the like; R 3 represents an optionally protected hydroxyl group or the like; R 4 represents an optionally substituted cycloalkyloxy group or the like; and R 5 represents a hydrogen atom or the like.)

摘要翻译： 本发明公开了使用或由通式（I）表示的二苯甲酮衍生物在组合它们的盐和一种或多种免疫抑制剂，以及含有该二苯甲酮衍生物或其盐和一种或多种免疫抑制剂的药物组合物。 的使用和该组合物是用于治疗或预防自身免疫性疾病的等是有用的。 （式中，R 1 darstellt到任选取代的杂环基，取代的苯基或类似物; Z darstellt在亚烷基等; R 2表示羧基基团，其可通过在烷基保护，或类似 ，R 3 darstellt到任选保护的羟基基团等; R 4 darstellt到任选取代的环烷氧基等;且R 5表示氢原子等）。

公开(公告)号：EP0695547B1

公开(公告)日：2001-08-08

申请号：EP94912070.3

申请日：1994-04-07

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： TANAKA, Keiichi ,  MAKINO, Shinji ,  OSHIO, Ichiro ,  SHIMOTORI, Tomoya ,  AIKAWA, Yukihiko ,  INABA, Takihiro ,  YOSHIDA, Chosaku ,  TAKANO, Shuntaro ,  TANIGUCHI, Yoichi

IPC分类号： A61K31/353 ,  A61K31/352 ,  C07D311/22

CPC分类号： C07D311/26 ,  C07D311/22 ,  C07D311/24

摘要： A 4H-1-benzopyran-4-one derivative of general formula [1], or a salt thereof exerts excellent effects of immunomodulation and cell adhesion inhibition, and is further expected to have the effect of relieving autoimmune diseases at a level comparable to that of steroids. Thus the compound of general formula [1] is useful in the treatment and prevention of autoimmune diseases fundamentally caused by immunopathy or abnormally accelerated cell adhesion, for example, chronic rheumatoid arthritis, systemic lupus erythematosus, sclerema, mixed connective tissue disease, polyarteritis nodosa, polymyositis/dermatomyositis, Sjögren's syndrome, Behcet's disease, multiple sclerosis, autoimmune diabetes, Hashimoto's disease, psoriasis, primary myxedema, pernicious anemia, serious adynamia, ulcerative colitis, chronic active hepatitis, autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.

公开(公告)号：EP1445249B1

公开(公告)日：2012-11-07

申请号：EP02781763.4

申请日：2002-11-13

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： CHAKI, Hisaaki ,  KOTSUBO, Hironori ,  TANAKA, Tadashi ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC分类号： C07C59/90 ,  C07C69/734 ,  C07C69/76 ,  C07C205/34 ,  C07C219/32 ,  C07C255/54 ,  C07C255/37 ,  C07C271/64 ,  C07C235/42 ,  C07C311/29 ,  C07C311/51 ,  C07D333/56 ,  C07D333/38 ,  C07D409/12 ,  C07D239/96 ,  C07D261/20 ,  A61K31/192 ,  A61P29/00

CPC分类号： C07C235/42 ,  A61K31/192 ,  C07C59/90 ,  C07C65/34 ,  C07C65/40 ,  C07C69/738 ,  C07C69/76 ,  C07C69/88 ,  C07C69/94 ,  C07C205/34 ,  C07C217/76 ,  C07C255/54 ,  C07C259/10 ,  C07C271/64 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/18

公开(公告)号：EP2258361A1

公开(公告)日：2010-12-08

申请号：EP09724165.7

申请日：2009-03-25

申请人： Toyama Chemical Co., Ltd.

发明人： AIKAWA, Yukihiko ,  SHIOZAWA, Shunichi

IPC分类号： A61K31/12 ,  A61K31/194 ,  A61K31/423 ,  A61K31/5377 ,  A61K39/395 ,  A61K45/00 ,  A61K45/06 ,  A61P1/00 ,  A61P1/16 ,  A61P13/12 ,  A61P19/02 ,  A61P29/00 ,  A61P37/02 ,  A61P37/06 ,  A61P43/00 ,  C07D261/20

CPC分类号： A61K31/12 ,  A61K31/194 ,  A61K31/423 ,  A61K31/5377 ,  A61K39/3955 ,  A61K45/06 ,  C07D261/20 ,  C07K16/241 ,  A61K2300/00

摘要： Disclosed are use of a benzophenone derivative represented by general formula (I) or a salt thereof and one or more TNFα inhibitors in combination, and a pharmaceutical composition containing the benzophenone derivative or a salt thereof and one or more TNFα inhibitors. The use and the composition are useful for treatment or prevention of autoimmune diseases and the like. (In the formula, R 1 represents an optionally substituted heterocyclic group, a substituted phenyl group or the like; Z represents an alkylene group or the like; R 2 represents a carboxyl group, which may be protected by an alkyl group, or the like; R 3 represents an optionally protected hydroxyl group or the like; R 4 represents an optionally substituted cycloalkyloxy group or the like; and R 5 represents a hydrogen atom or the like.)

摘要翻译： 本发明公开了使用或由通式（I）表示的二苯甲酮衍生物的盐和一种或多种TNF±组合抑制剂，以及含有该二苯甲酮衍生物或其盐和一种或多种TNF±抑制剂的药物组合物。 的使用和该组合物是用于治疗或预防自身免疫性疾病的等是有用的。 （式中，R 1 darstellt到任选取代的杂环基，取代的苯基或类似物; Z darstellt在亚烷基等; R 2表示羧基基团，其可通过在烷基保护，或类似 ，R 3 darstellt到任选保护的羟基基团等; R 4 darstellt到任选取代的环烷氧基等;且R 5表示氢原子等）。

公开(公告)号：EP1076056A1

公开(公告)日：2001-02-14

申请号：EP99918266.0

申请日：1999-04-28

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： CHAKI, Hisaaki ,  AIKAWA, Yukihiko ,  MIYAJIMA, Mikako ,  TAKAKURA, Tadakazu ,  NISHIO, Morihiro ,  KURODA, Hiroshi ,  TANAKA, Keiichi ,  KAJITA, Tetsuya ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC分类号： C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10 ,  C07K5/04 ,  A61K31/425 ,  A61K31/44 ,  A61K31/445 ,  A61K38/04

CPC分类号： C07D277/60 ,  A61K38/00 ,  C07D417/04 ,  C07D417/06 ,  C07D417/08 ,  C07D417/12 ,  C07D513/10 ,  C07K5/06139

摘要： The spiro compounds of the present invention represented by the following general formula:
wherein A, R 2 , R 3 , R 4 , R 5 , R 6 and n are as defined in the specification, exhibit an AP-1 activity inhibitory action and, based on the AP-1 inhibitory action, suppresses the expression of a wide variety of genes and are useful as an agent for treating and preventing autoimmune diseases with lessened side reactions.

摘要翻译： 如在定义 worin A，R <2> [R <3>，R <4> - [R <5> - [R <6>和n：由下述通式表示的本发明的螺环化合物 AP-1活性抑制作用的说明书中，表现出和，基于AP-1抑制作用，抑制了各种基因的表达，并且作为用于治疗和减轻与副反应预防自身免疫性疾病的药剂是有用的。

公开(公告)号：EP0695547A1

公开(公告)日：1996-02-07

申请号：EP94912070.3

申请日：1994-04-07

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： TANAKA, Keiichi ,  MAKINO, Shinji ,  OSHIO, Ichiro ,  SHIMOTORI, Tomoya ,  AIKAWA, Yukihiko ,  INABA, Takihiro ,  YOSHIDA, Chosaku ,  TAKANO, Shuntaro ,  TANIGUCHI, Yoichi

IPC分类号： A61K31/35 ,  A61K31/38 ,  A61K31/40 ,  A61K31/41 ,  A61K31/44 ,  A61K31/445 ,  C07D311/24 ,  C07D311/26 ,  C07D311/44 ,  C07D311/54 ,  C07D311/56

CPC分类号： C07D311/26 ,  C07D311/22 ,  C07D311/24

摘要： A 4H-1-benzopyran-4-one derivative of general formula [1], or a salt thereof exerts excellent effects of immunomodulation and cell adhesion inhibition, and is further expected to have the effect of relieving autoimmune diseases at a level comparable to that of steroids. Thus the compound of general formula [1] is useful in the treatment and prevention of autoimmune diseases fundamentally caused by immunopathy or abnormally accelerated cell adhesion, for example, chronic rheumatoid arthritis, systemic lupus erythematosus, sclerema, mixed connective tissue disease, polyarteritis nodosa, polymyositis/dermatomyositis, Sjögren's syndrome, Behcet's disease, multiple sclerosis, autoimmune diabetes, Hashimoto's disease, psoriasis, primary myxedema, pernicious anemia, serious adynamia, ulcerative colitis, chronic active hepatitis, autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.

摘要翻译： 的4H-1-苯并吡喃-4-酮通式A1U的衍生物，或其盐发挥免疫调节和细胞粘附抑制的优异的效果，并且进一步预期具有在一个水平减轻自身免疫性疾病媲美做类固醇的效果 ， THUS通式A1U的化合物在治疗和预防由免疫疾病从根本上引起的自身免疫疾病或异常加速细胞粘附，例如，慢性类风湿性关节炎，系统性红斑狼疮，硬肿症，混合性结缔组织病，结节性多动脉炎，多肌炎/有用 皮肌炎，干燥综合征，贝切特氏病，多发性硬化症，自身免疫性糖尿病，桥本氏病，牛皮癣，原发性粘液水肿，恶性贫血，严重动力缺乏，溃疡性结肠炎，慢性活动性肝炎，自身免疫性溶血性贫血和特发性血小板减少性紫癜。

公开(公告)号：EP2258361B1

公开(公告)日：2014-09-17

申请号：EP09724165.7

申请日：2009-03-25

申请人： Toyama Chemical Co., Ltd.

发明人： AIKAWA, Yukihiko ,  SHIOZAWA, Shunichi

IPC分类号： A61K31/12 ,  A61K31/194 ,  A61K31/423 ,  A61K31/5377 ,  A61K39/395 ,  A61K45/00 ,  A61K45/06 ,  A61P1/00 ,  A61P1/16 ,  A61P13/12 ,  A61P19/02 ,  A61P29/00 ,  A61P37/02 ,  A61P37/06 ,  A61P43/00 ,  C07D261/20

CPC分类号： A61K31/12 ,  A61K31/194 ,  A61K31/423 ,  A61K31/5377 ,  A61K39/3955 ,  A61K45/06 ,  C07D261/20 ,  C07K16/241 ,  A61K2300/00

公开(公告)号：EP2266557B1

公开(公告)日：2013-08-14

申请号：EP09735250.4

申请日：2009-04-20

申请人： Toyama Chemical Co., Ltd.

发明人： AIKAWA, Yukihiko ,  SHIOZAWA, Shunichi

IPC分类号： A61K31/194 ,  A61K31/42 ,  A61K31/423 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/573 ,  A61K45/06 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00

CPC分类号： A61K45/06 ,  A61K31/194 ,  A61K31/42 ,  A61K31/423 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/573 ,  A61K2300/00

公开(公告)号：EP1445249A1

公开(公告)日：2004-08-11

申请号：EP02781763.4

申请日：2002-11-13

申请人： TOYAMA CHEMICAL CO., LTD. ,  Hirono, Shuichi ,  Shiozawa, Shunichi

发明人： CHAKI, Hisaaki ,  KOTSUBO, Hironori ,  TANAKA, Tadashi ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC分类号： C07C59/90 ,  C07C69/734 ,  C07C69/76 ,  C07C205/34 ,  C07C219/32 ,  C07C255/54 ,  C07C255/37 ,  C07C271/64 ,  C07C235/42 ,  C07C311/29 ,  C07C311/51 ,  C07C311/53 ,  C07C317/22 ,  C07C323/19 ,  A61K31/192

CPC分类号： C07C235/42 ,  A61K31/192 ,  C07C59/90 ,  C07C65/34 ,  C07C65/40 ,  C07C69/738 ,  C07C69/76 ,  C07C69/88 ,  C07C69/94 ,  C07C205/34 ,  C07C217/76 ,  C07C255/54 ,  C07C259/10 ,  C07C271/64 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/18

摘要： A benzophenone derivative represented by the following formula:
wherein

R 1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R 2 represents, for example, a carboxyl group optionally protected with alkyl;
R 3 represents, for example, an optionally protected hydroxyl group; R 4 represents, for example, an optionally substituted cycloalkyloxy group; and R 5 represents, for example, a hydrogen atom,
   or a salt thereof has anti-arthritic activity, inhibits bone destruction caused by arthritis, and provides high safety and excellent pharmacokinetics and thus is useful as therapeutic agent for arthritis. These compounds have inhibitory effect on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression of AP-1 is involved.

公开(公告)号：EP1127869A1

公开(公告)日：2001-08-29

申请号：EP99954398.6

申请日：1999-11-05

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： CHAKI, Hisaaki ,  TAKAKURA, Tadakazu ,  TSUCHIDA, Keiichi ,  YOKOTANI, Junichi ,  KOTSUBO, Hironori ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC分类号： C07C69/73 ,  C07C69/767 ,  C07C205/49

CPC分类号： C07D207/333 ,  A61K38/00 ,  C07C59/64 ,  C07C59/84 ,  C07C65/24 ,  C07C65/34 ,  C07C65/36 ,  C07C65/38 ,  C07C65/40 ,  C07C69/738 ,  C07C69/94 ,  C07C229/34 ,  C07C233/01 ,  C07C233/47 ,  C07C235/20 ,  C07C235/84 ,  C07C251/32 ,  C07C251/48 ,  C07C251/60 ,  C07C255/49 ,  C07C275/24 ,  C07C311/06 ,  C07C311/51 ,  C07D207/08 ,  C07D209/42 ,  C07D235/26 ,  C07D277/60 ,  C07K7/06 ,  C07K7/64 ,  Y02P20/55

摘要： A compound comprising the atom corresponding to N 3 and the two or more atoms selected from N 1 , N 2 , N 4 and N 5 , said atoms constitute the pharmacophore represented by the following formula:
wherein N 1 represents an atom to which a donative hydrogen atom in a hydrogen-bond donating group is bonded or a hydrogen-bond accepting atom in a hydrogen-bond accepting group; N 3 represents a hydrogen-bond accepting atom in a hydrogen-bond accepting group; and N 2 , N 4 and N 5 independently represents an arbitrary carbon atom constituting a hydrophobic group and defined by the interatomic distances between N 1 , N 2 , N 3 , N 4 and N 5 ; and, in the optimized three-dimensional structure thereof, the distances between the atom corresponding to N 3 and the two or more atoms selected from N 1 , N 2 , N 4 and N 5 , in the optimized steric structure thereof, are the interatomic distances in a pharmacophore; or a salt thereof;
   inhibits the activity of transcription factor AP-1 and is useful as an agent for preventing and treating the diseases into which overexpression of AP-1 participates and as an AP-1 inhibitor.

摘要翻译： 包含对应于N 3的原子和选自N1，N2，N4和N5的两个或更多个原子的化合物，所述原子构成由下式表示的药效团：其中N1表示与 在氢键接受基团中键合氢键供体基团或氢键接受原子; N3表示氢键接受基团中的氢键接受原子; N2，N4和N5独立地表示构成疏水基团的任意碳原子，由N1，N2，N3，N4和N5之间的原子间距离定义; 并且在其优化的三维结构中，在其优化的立体结构中，对应于N 3的原子与选自N1，N2，N4和N5的两个或更多个原子之间的距离是药效团中的原子间距离; 或其盐; 抑制转录因子AP-1的活性，可用作预防和治疗AP-1过表达的疾病和作为AP-1抑制剂的药物。