公开(公告)号：US20070270429A1

公开(公告)日：2007-11-22

申请号：US10555611

申请日：2004-04-28

申请人： Shiro Shibayama ,  Tetsuya Sugiyama ,  Kenji Sagawa ,  Miki Kasano

发明人： Shiro Shibayama ,  Tetsuya Sugiyama ,  Kenji Sagawa ,  Miki Kasano

IPC分类号： A61K31/498

CPC分类号： C07D471/10 ,  A61K31/499 ,  A61K45/06

摘要： The present invention relates to a function inhibitor of an effector cell comprising a CCR5 antagonist. Since the function inhibitor of an effector cell comprising a CCR5 antagonist inhibits the function of effector cells which play an important role in formation of diseases and the like, it is effective for the prevention and/or treatment of, for example, a transplant rejection (e.g., rejection of a solid organ graft, rejection of islet cell transplantation in diabetes mellitus, graft-versus-host disease (GVHD), etc.), an autoimmune disease (e.g., arthritis, rheumatoid arthritis, multiple sclerosis, ulcerative colitis, etc.), an allergic disease (e.g., asthma, etc.), an ischemic disease (e.g., ischemia-reperfusion injury, etc.), cancer or a metastatic disease or the like.

摘要翻译： 本发明涉及包含CCR5拮抗剂的效应细胞的功能抑制剂。 由于包含CCR5拮抗剂的效应细胞的功能抑制剂抑制在疾病形成等中起重要作用的效应细胞的功能，所以有效预防和/或治疗例如移植排斥反应（ 例如，实体器官移植排斥反应，糖尿病胰岛细胞移植排斥反应，移植物抗宿主病（GVHD）等），自身免疫性疾病（例如关节炎，类风湿性关节炎，多发性硬化症，溃疡性结肠炎等） ），过敏性疾病（例如哮喘等），缺血性疾病（例如缺血再灌注损伤等），癌症或转移性疾病等。

公开(公告)号：US08476290B2

公开(公告)日：2013-07-02

申请号：US13378799

申请日：2010-06-15

申请人： Koji Yoshida ,  Hiroshi Ochiai ,  Kousuke Tani ,  Shiro Shibayama ,  Miki Kasano

发明人： Koji Yoshida ,  Hiroshi Ochiai ,  Kousuke Tani ,  Shiro Shibayama ,  Miki Kasano

IPC分类号： A61K31/438 ,  C07D471/10

CPC分类号： C07D471/10

摘要： A compound represented by formula (I): a salt thereof, an N-oxide thereof, or a solvate thereof (symbols in the formula are as described in the specification). The compounds of the present invention exhibit very low risk of side effects and also have persistent and strong antagonistic activity against CXCR4, and are therefore useful as pharmaceuticals, for example, as a preventive and/or therapeutic agent for inflammatory and immune diseases, infections (for example, HIV infection), diseases associated with HIV infection (for example, acquired immunodeficiency syndrome (AIDS)), cancer, cancer metastasis, psychoneurotic diseases and cardiovascular diseases (for example, retinopathy), metabolic diseases, cancerous diseases, or as an agent for regeneration therapy.

摘要翻译： 由式（I）表示的化合物：其盐，其N-氧化物或其溶剂化物（式中的符号如说明书中所述）。 本发明的化合物显示出非常低的副作用风险，并且对CXCR4具有持久和强烈的拮抗活性，因此可用作药物，例如作为炎症和免疫疾病，感染的预防和/或治疗剂（ 例如艾滋病毒感染），与艾滋病毒感染有关的疾病（例如，获得性免疫缺陷综合征（AIDS）），癌症，癌症转移，精神神经病和心血管疾病（例如视网膜病变），代谢疾病，癌性疾病或作为 再生治疗剂。

公开(公告)号：US20120101280A1

公开(公告)日：2012-04-26

申请号：US13378799

申请日：2010-06-15

申请人： Koji Yoshida ,  Hiroshi Ochiai ,  Kousuke Tani ,  Shiro Shibayama ,  Miki Kasano

发明人： Koji Yoshida ,  Hiroshi Ochiai ,  Kousuke Tani ,  Shiro Shibayama ,  Miki Kasano

IPC分类号： C07D471/10

CPC分类号： C07D471/10

摘要： The invention relates to a compound represented by formula (I): a salt thereof, an N-oxide thereof, or a solvate thereof (symbols in the formula are as described in the specification).The compound of the present invention exhibits very low risk of side effects and also has persistent and strong antagonistic activity against CXCR4, and is therefore useful as pharmaceuticals, for example, preventive and/or therapeutic agent for inflammatory and immune diseases, infections (for example, HIV infection), diseases associated with HIV infection (for example, acquired immunodeficiency syndrome (AIDS)), cancer, cancer metastasis, psychoneurotic diseases and cardiovascular diseases (for example, retinopathy), metabolic diseases, cancerous diseases, or an agent for regeneration therapy.

摘要翻译： 本发明涉及由式（I）表示的化合物：其盐，其N-氧化物或其溶剂化物（式中的符号如说明书中所述）。 本发明的化合物显示出非常低的副作用风险，并且对CXCR4具有持久和强烈的拮抗活性，因此可用作药物，例如用于炎症和免疫疾病，感染的预防和/或治疗剂（例如 ，艾滋病毒感染），与艾滋病毒感染有关的疾病（例如，获得性免疫缺陷综合征（AIDS）），癌症，癌症转移，精神神经病和心血管疾病（例如视网膜病变），代谢疾病，癌性疾病或再生药剂 治疗。

公开(公告)号：US20060004010A1

公开(公告)日：2006-01-05

申请号：US10520660

申请日：2003-07-08

申请人： Hiromu Habashita ,  Masaya Kokubo ,  Shiro Shibayama ,  Hideaki Tada ,  Kenji Sagawa

发明人： Hiromu Habashita ,  Masaya Kokubo ,  Shiro Shibayama ,  Hideaki Tada ,  Kenji Sagawa

IPC分类号： A61K31/498 ,  C07D43/14

CPC分类号： C07D409/12 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61K31/506 ,  A61K31/55 ,  C07D241/22 ,  C07D241/26 ,  C07D241/44 ,  C07D401/12

摘要： A compound of formula (I) or a salt thereof, and medical use thereof (the symbols in the formula are as described in the specification). The compound of formula (I) has CCR4 antagonistic activity, and therefore is useful as a preventive and/or therapeutic agent for diseases associated with CCR4, i.e., CCR4-mediated diseases such as inflammatory and/or allergic diseases [e.g., systemic inflammatory response syndrome (SIRS), anaphylaxis or anaphylaxis-like reaction, allergic vasculitis, reject reaction for graft organ, hepatitis, nephritis, nephrosis, pancreatitis, rhinitis, arthritis, inflammatory ocular diseases, inflammatory bowel diseases, diseases in cerebro and/or circulatory system, respiratory diseases, dermatic diseases, autoimmune diseases, etc.], and the like.

摘要翻译： 式（I）化合物或其盐及其医疗用途（式中的符号如说明书中所述）。 式（I）化合物具有CCR4拮抗活性，因此可用作与CCR4相关的疾病的预防和/或治疗剂，即CCR4介导的疾病如炎性和/或过敏性疾病[例如全身炎症反应 综合征（SIRS），过敏反应或过敏反应，过敏性血管炎，移植器官排斥反应，肝炎，肾炎，肾病，胰腺炎，鼻炎，关节炎，炎性眼部疾病，炎性肠病，脑脊液和/或循环系统疾病， 呼吸系统疾病，皮肤病，自身免疫性疾病等]等。

公开(公告)号：US20060251651A1

公开(公告)日：2006-11-09

申请号：US10538364

申请日：2003-12-12

申请人： Shiro Shibayama ,  Kenji Sagawa ,  Noriki Watanabe ,  Kazuhiko Takeda ,  Hideaki Tada ,  Daikichi Fukushima

发明人： Shiro Shibayama ,  Kenji Sagawa ,  Noriki Watanabe ,  Kazuhiko Takeda ,  Hideaki Tada ,  Daikichi Fukushima

IPC分类号： A61K39/395 ,  G01N33/567 ,  C07K16/28

CPC分类号： A61K31/49 ,  A61K31/00 ,  A61K31/503 ,  A61K31/5377 ,  G01N2333/715 ,  G01N2500/04

摘要： An antagonist or an agonist which binds to a strong binding site of CCR5; a preventive and/or therapeutic agent for an allergic disease, an inflammatory disease, an immune disease and/or a cancer which comprises the same; a method for screening a compound which binds to a strong binding site of CCR5; a preventive and/or therapeutic agent for an allergic disease, an inflammatory disease, an immune disease and/or a cancer which comprises the antagonist or the agonist selected by the screening method; an antagonist or an agonist which binds to a strong binding site of a chemokine receptor; a preventive and/or therapeutic agent for an allergic disease, an inflammatory disease, an immune disease and/or a cancer which comprises the same; a method for screening a compound which binds to a strong binding site of a chemokine receptor; and a preventive and/or therapeutic agent for an allergic disease, an inflammatory disease, an immune disease and/or a cancer which comprises the antagonist or the agonist selected by the screening method. The antagonist or the agonist of the present invention is useful as a preventive and/or therapeutic agent for an allergic disease, an inflammatory disease, an immune disease and/or a cancer.

摘要翻译： 结合CCR5的强结合位点的拮抗剂或激动剂; 用于过敏性疾病，炎性疾病，免疫疾病和/或包含该疾病的癌症的预防和/或治疗剂; 用于筛选结合CCR5的强结合位点的化合物的方法; 包含通过筛选方法选择的拮抗剂或激动剂的过敏性疾病，炎性疾病，免疫疾病和/或癌症的预防和/或治疗剂; 结合趋化因子受体的强结合位点的拮抗剂或激动剂; 用于过敏性疾病，炎性疾病，免疫疾病和/或包含该疾病的癌症的预防和/或治疗剂; 用于筛选结合趋化因子受体的强结合位点的化合物的方法; 以及包含通过筛选方法选择的拮抗剂或激动剂的过敏性疾病，炎性疾病，免疫疾病和/或癌症的预防和/或治疗剂。 本发明的拮抗剂或激动剂可用作过敏性疾病，炎性疾病，免疫疾病和/或癌症的预防和/或治疗剂。

公开(公告)号：US20050267114A1

公开(公告)日：2005-12-01

申请号：US10527435

申请日：2003-09-17

申请人： Yoshikazu Takaoka ,  Rena Nishizawa ,  Shiro Shibayama ,  Kenji Sagawa ,  Masayoshi Matsuo

发明人： Yoshikazu Takaoka ,  Rena Nishizawa ,  Shiro Shibayama ,  Kenji Sagawa ,  Masayoshi Matsuo

IPC分类号： A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P9/00 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P13/12 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P27/00 ,  A61P29/00 ,  A61P31/04 ,  A61P31/18 ,  A61P35/04 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D471/10 ,  A61K31/498 ,  C07D487/10

CPC分类号： C07D471/10

摘要： Compounds represented by formula (I) (wherein all of the symbols have the same meanings as defined in specification.), quaternary ammonium salts thereof, N-oxides thereof or salts thereof. The compounds represented by formula (I) are used for prevention and/or treatment of various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, chronic rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis and the like), immunologic diseases (autoimmune diseases, transplant rejection, immunosuppression, psoriasis, multiple sclerosis and the like), human immunodeficiency virus (acquired immunodeficiency syndrome and the like), allergic diseases (atopic dermatitis, nettle rash, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis and the like), ischemia-reperfusion injury, acute respiratory distress syndrome, shock accompanied by bacterial infection, diabetes mellitus, or metastasis and the like.

摘要翻译： 由式（I）表示的化合物（其中所有符号具有与说明书中所定义的相同的含义），其季铵盐，其N-氧化物或其盐。 由式（I）表示的化合物用于预防和/或治疗各种炎性疾病（哮喘，肾炎，肾病，肝炎，关节炎，慢性类风湿性关节炎，鼻炎，结膜炎，溃疡性结肠炎等），免疫疾病 疾病，移植排斥反应，免疫抑制，牛皮癣，多发性硬化等），人类免疫缺陷病毒（获得性免疫缺陷综合征等），过敏性疾病（特应性皮炎，荨麻疹，过敏性支气管肺曲霉病，过敏嗜酸性胃肠炎等），局部缺血 再灌注损伤，急性呼吸窘迫综合征，伴有细菌感染的休克，糖尿病或转移等。

公开(公告)号：US08951518B2

公开(公告)日：2015-02-10

申请号：US13548807

申请日：2012-07-13

申请人： Tasuku Honjo ,  Shiro Shibayama ,  Kazuhiko Takeda ,  Masayoshi Matsuo ,  Takao Yoshida ,  Masakazu Miyamoto

发明人： Tasuku Honjo ,  Shiro Shibayama ,  Kazuhiko Takeda ,  Masayoshi Matsuo ,  Takao Yoshida ,  Masakazu Miyamoto

IPC分类号： A61K39/395 ,  C07K16/28 ,  A61K39/00

CPC分类号： C07K16/2818 ,  A61K39/3955 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/73

摘要： The present invention relates to a substance specific to human PD-1 comprising a part that recognizes human PD-1, a part that recognizes a membrane protein in cell membrane of human PD-1-expressing cells, and linkers. Since the substance specific to human PD-1 selectively can recognize human PD-1 and a membrane protein on cell membrane of human PD-1-expressing cells and can transmit inhibitory signal of human PD-1, it is useful for therapy and/or prevention of diseases caused by immunopathy.

公开(公告)号：US08822459B2

公开(公告)日：2014-09-02

申请号：US13027957

申请日：2011-02-15

申请人： Masaya Kokubo ,  Yoshikazu Takaoka ,  Shiro Shibayama

发明人： Masaya Kokubo ,  Yoshikazu Takaoka ,  Shiro Shibayama

IPC分类号： A61K31/535 ,  C07D265/28 ,  C07D471/10 ,  C07D233/90 ,  C07D401/14 ,  C07D487/10 ,  C07D233/16 ,  C07D233/84 ,  C07D403/12 ,  C07D403/14

CPC分类号： C07D471/10 ,  C07D233/16 ,  C07D233/84 ,  C07D233/90 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D487/10

摘要： The present invention relates to a compound represented by formula (I-0): wherein symbols in formula have the same meanings as described in the present specification, a salt thereof, an N-oxide thereof or a solvate thereof or a prodrug thereof, and medical use thereof. The compound of the present invention has an antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, retinopathy, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiovascular disease, metabolic diseases, and cancerous diseases (for example, cancer, cancer metastasis, etc.), or an agent for regeneration therapy.

摘要翻译： 本发明涉及由式（I-0）表示的化合物：其中式中的符号与本说明书中所述的相同含义，其盐，其N-氧化物或其溶剂合物或其前药，以及 医疗用途。 本发明的化合物对CXCR4具有拮抗作用，因此可用作CXCR4介导的疾病的预防和/或治疗剂，例如炎性和免疫疾病（例如类风湿性关节炎，关节炎，视网膜病变，肺纤维化 ，移植器官排斥反应等），过敏性疾病，感染（例如人类免疫缺陷病毒感染，获得性免疫缺陷综合征等），精神神经病，脑疾病，心血管疾病，代谢疾病和癌性疾病（例如癌症 ，癌转移等）或再生治疗剂。

公开(公告)号：US08618122B2

公开(公告)日：2013-12-31

申请号：US12301194

申请日：2007-05-15

申请人： Kensuke Kusumi ,  Masaya Kokubo ,  Hiroshi Ochiai ,  Shiro Shibayama

发明人： Kensuke Kusumi ,  Masaya Kokubo ,  Hiroshi Ochiai ,  Shiro Shibayama

IPC分类号： A61K31/44 ,  A61K31/415 ,  C07D215/00 ,  C07D233/00

CPC分类号： C07D471/10

摘要： A compound represented by general formula (I): a salt thereof, a solvate thereof, or a prodrug thereof wherein all symbols are as defined in the specification. The compound of the present invention has antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, systemic erythematosus, retinopathy, macular degeneration, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiovascular disease, metabolic diseases, cancerous diseases (for example, cancer, cancer metastasis, etc.), or an agent for regeneration therapy.

摘要翻译： 由通式（I）表示的化合物：其盐，其溶剂合物或其前药，其中所有符号如说明书中所定义。 本发明的化合物对CXCR4具有拮抗作用，因此可用作CXCR4介导的疾病的预防和/或治疗剂，例如炎性和免疫疾病（例如类风湿性关节炎，关节炎，全身性红斑狼疮，视网膜病变， 黄斑变性，肺纤维化，移植器官排斥反应等），过敏性疾病，感染（例如人类免疫缺陷病毒感染，获得性免疫缺陷综合征等），精神神经病，脑疾病，心血管疾病，代谢疾病，癌性疾病 例如癌症，癌症转移等）或再生治疗剂。

公开(公告)号：US08519124B2

公开(公告)日：2013-08-27

申请号：US13415399

申请日：2012-03-08

申请人： Masaya Kokubo ,  Hiroshi Ochiai ,  Yoshikazu Takaoka ,  Shiro Shibayama

发明人： Masaya Kokubo ,  Hiroshi Ochiai ,  Yoshikazu Takaoka ,  Shiro Shibayama

IPC分类号： C07D221/20 ,  C07D265/14 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14

CPC分类号： C07D403/12 ,  C07D233/64 ,  C07D401/12 ,  C07D403/14 ,  C07D471/10 ,  C07D498/10

摘要： A compound represented by general formula (I): a salt thereof, a solvate thereof, or a prodrug thereof wherein all symbols are as defined in the specification has an antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, systemic erythematosus, retinopathy, macular degeneration, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiac/vascular disease (for example, arteriosclerosis, myocardial infarction, stenocardia, cerebral infarction, chronic arterial occlusive disease, etc.), metabolic diseases, and cancerous diseases (for example, cancer, cancer metastasis, etc.), a preventive and/or therapeutic agent for cancerous diseases or infections, or an agent for regeneration therapy.

摘要翻译： 由通式（I）表示的化合物：其盐，其溶剂化物或前药，其中所有符号如本说明书中所定义，具有对CXCR4的拮抗活性，因此可用作预防和/或治疗剂 CXCR4介导的疾病，例如炎症和免疫疾病（例如类风湿性关节炎，关节炎，全身性红斑狼疮，视网膜病变，黄斑变性，肺纤维化，移植器官排斥反应等），过敏性疾病，感染（例如人类免疫缺陷 病毒感染，获得性免疫缺陷综合征等），精神神经病，脑疾病，心脏/血管疾病（例如动脉硬化，心肌梗塞，心动过速，脑梗死，慢性动脉闭塞性疾病等），代谢疾病和癌性疾病 （例如，癌症，癌症转移等），癌性疾病或感染的预防和/或治疗剂， 或再生治疗剂。