公开(公告)号：US20120165309A1

公开(公告)日：2012-06-28

申请号：US13201072

申请日：2010-02-10

申请人： Fumie Takahashi ,  Sunao Imada ,  Masahiko Shiwaku ,  Yasumasa Shiwaku ,  Atsuko Shiwaku ,  Koji Kato ,  Hidehiko Fukahori

发明人： Fumie Takahashi ,  Sunao Imada ,  Masahiko Shiwaku ,  Yasumasa Shiwaku ,  Atsuko Shiwaku ,  Koji Kato ,  Hidehiko Fukahori

IPC分类号： A61K31/5377 ,  C07D417/14 ,  A61P35/00 ,  A61P37/06 ,  A61P37/08 ,  A61P37/00 ,  C07D413/14 ,  A61K31/541

CPC分类号： A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： [Object]A novel and excellent method for preventing or treating rejection in the transplantation of various organs, allergy diseases, autoimmune diseases, hematologic tumor, or the like, based on a PI3Kδ-selective inhibitory action and/or an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action (including an activation inhibitory action), is provided[Means for Solution]It was found that a 3-substituted triazine or 3-substituted pyrimidine derivative exhibits a PI3Kδ-selective inhibitory action, and/or an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action (including an activation inhibitory action), and can be an agent for preventing or treating rejection in the transplantation of various organs, allergy diseases (asthma, atopic dermatitis, etc.), autoimmune diseases (rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, etc.), hematologic tumor (leukemia etc.), or the like, thereby completing the present invention.

摘要翻译： [目的]基于PI3Kδ选择性抑制作用和/或IL-2产生抑制作用，预防或治疗各种器官，过敏性疾病，自身免疫性疾病，血液肿瘤等的移植中的排斥反应的新颖且优异的方法 提供了作用和/或B细胞增殖抑制作用（包括活化抑制作用）[解决方案]发现3-取代的三嗪或3-取代的嘧啶衍生物显示出PI3Kδ选择性抑制作用，并且 /或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括活化抑制作用），并且可以是用于预防或治疗各种器官移植排斥反应的药物，过敏疾病（哮喘，特应性 皮炎等），自身免疫性疾病（类风湿性关节炎，牛皮癣，溃疡性结肠炎，克罗恩病，系统性红斑狼疮等），血液肿瘤（白血病等）等，t 从而完成本发明。

公开(公告)号：US20110230467A1

公开(公告)日：2011-09-22

申请号：US13130527

申请日：2009-11-20

申请人： Shohei Shirakami ,  Fumie Takahashi ,  Yutaka Nakajima ,  Hirofumi Omura ,  Naohiro Aoyama ,  Hiroshi Sasaki ,  Takeshi Hondo ,  Hiroaki Tominaga

发明人： Shohei Shirakami ,  Fumie Takahashi ,  Yutaka Nakajima ,  Hirofumi Omura ,  Naohiro Aoyama ,  Hiroshi Sasaki ,  Takeshi Hondo ,  Hiroaki Tominaga

IPC分类号： A61K31/55 ,  A61K31/5513 ,  A61K31/5377 ,  A61P43/00 ,  A61K31/497 ,  A61K31/506 ,  A61K31/444 ,  A61K31/4439 ,  C07D401/14 ,  C07D413/14 ,  C07D401/12 ,  C07D417/14 ,  C07D409/14 ,  C07D401/00

CPC分类号： C07D401/12 ,  C07D213/82 ,  C07D401/14 ,  C07D405/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10

摘要： [Problem] The present invention provides a 4,6-diaminonicotinamide compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for treating diseases caused by undesirable and/or abnormal cytokine signal transduction.[Means for Solution] The present inventors have extensively studied compounds having a JAK3 inhibitory action, and as a result, they have found that a 4,6-diaminonicotinamide compound which is the compound of the present invention has an excellent JAK3 inhibitory action and is useful as an agent for preventing or treating diseases caused by undesirable and/or abnormal cytokine signal transduction, thereby completing the present invention.

摘要翻译： 本发明提供了可用作药物组合物的活性成分的特征的4,6-二氨基烟酰胺化合物，特别是用于治疗由不希望的和/或异常的细胞因子信号转导引起的疾病的药物组合物。 [解决方案]本发明人广泛研究了具有JAK3抑制作用的化合物，结果发现作为本发明化合物的4,6-二氨基烟酰胺化合物具有优异的JAK3抑制作用， 可用作预防或治疗由不良和/或异常细胞因子信号转导引起的疾病的药剂，从而完成本发明。

公开(公告)号：US20110039822A1

公开(公告)日：2011-02-17

申请号：US12914475

申请日：2010-10-28

申请人： Takayuki INOUE ,  Akira Tanaka ,  Kazuo Nakai ,  Hiroshi Sasaki ,  Fumie Takahashi ,  Shohei Shirakami ,  Keiko Hatanaka ,  Yutaka Nakajima ,  Koichiro Mukoyoshi ,  Hisao Hamaguchi ,  Shigeki Kunikawa ,  Yasuyuki Higashi

发明人： Takayuki INOUE ,  Akira Tanaka ,  Kazuo Nakai ,  Hiroshi Sasaki ,  Fumie Takahashi ,  Shohei Shirakami ,  Keiko Hatanaka ,  Yutaka Nakajima ,  Koichiro Mukoyoshi ,  Hisao Hamaguchi ,  Shigeki Kunikawa ,  Yasuyuki Higashi

IPC分类号： A61K31/437 ,  C07D471/04 ,  C07D471/14 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61P17/06 ,  A61P19/02 ,  A61P37/00 ,  A61P37/06

CPC分类号： C07D451/04 ,  C07D471/04 ,  C07D471/14 ,  C07D519/00

摘要： The present invention provides a compound having an excellent JAK3 inhibition activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases, inflammatory diseases, and allergic diseases.As a result of studies on a novel condensed heterocyclic derivative, the inventors have found that a compound having a cross-linked structure has an excellent JAK3 inhibition activity, and have completed the present invention.In other words, it is verified that the compound according to the present invention has an inhibition activity against JAK3 and is thus useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transmission (e.g., rejection during organ/tissue transplantation, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, atopic dermatitis, Alzheimer's disease, and atherosclerotic disease), or diseases caused by abnormal cytokine signal transmission (e.g., cancer and leukemia).

摘要翻译： 本发明提供具有优异的JAK3抑制活性的化合物，可用作治疗和/或预防各种免疫疾病，包括自身免疫性疾病，炎症性疾病和过敏性疾病的药剂的活性成分。 作为研究新型稠合杂环衍生物的结果，本发明人发现具有交联结构的化合物具有优异的JAK3抑制活性，并且完成了本发明。 换句话说，证实了本发明的化合物对JAK3具有抑制活性，因此可用作治疗或预防由不期望的细胞因子信号传导引起的疾病的药剂的活性成分（例如器官/ 组织移植，自身免疫性疾病，多发性硬化，类风湿性关节炎，牛皮癣，哮喘，特应性皮炎，阿尔茨海默病和动脉粥样硬化疾病）或由异常细胞因子信号传导引起的疾病（例如癌症和白血病）。

公开(公告)号：US20090264399A1

公开(公告)日：2009-10-22

申请号：US11995445

申请日：2006-07-13

申请人： Takayuki Inoue ,  Takashi Tojo ,  Masataka Morita ,  Yutaka Nakajima ,  Keiko Hatanaka ,  Shohei Shirakami ,  Hiroshi Sasaki ,  Akira Tanaka ,  Fumie Takahashi ,  Koichiro Mukoyoshi ,  Yasuyuki Higashi ,  Akira Okimoto ,  Takeshi Hondo ,  Hitoshi Sawada

发明人： Takayuki Inoue ,  Takashi Tojo ,  Masataka Morita ,  Yutaka Nakajima ,  Keiko Hatanaka ,  Shohei Shirakami ,  Hiroshi Sasaki ,  Akira Tanaka ,  Fumie Takahashi ,  Koichiro Mukoyoshi ,  Yasuyuki Higashi ,  Akira Okimoto ,  Takeshi Hondo ,  Hitoshi Sawada

IPC分类号： A61K31/437 ,  C07D471/04 ,  C07D413/14 ,  C07D471/14 ,  A61K31/5377 ,  A61K31/397 ,  A61P25/00 ,  A61P37/06 ,  A61P35/00 ,  A61P35/02 ,  A61P11/06

CPC分类号： C07D471/14 ,  C07D519/00

摘要： The invention relates to compound of the formula (I) or its salt, wherein —R1, —R2, —R3, —R4, —R5, -M-, —X— and —Y═ are as defined in the description, their use of as, medicament, the process for their preparation and use for the treatment of JAK3 mediated diseases.

摘要翻译： 本发明涉及式（I）或其盐的化合物，其中-R1，-R2，-R3，-R4，-R5，-M-，-X-和-Y-如说明书中所定义，它们 使用as，药物，其制备方法和用于治疗JAK3介导的疾病。

公开(公告)号：US06384028B1

公开(公告)日：2002-05-07

申请号：US08894795

申请日：1997-09-10

申请人： Mitsuru Ohkubo ,  Fumie Takahashi ,  Toshio Yamanaka ,  Masayuki Kato

发明人： Mitsuru Ohkubo ,  Fumie Takahashi ,  Toshio Yamanaka ,  Masayuki Kato

IPC分类号： C07D21136

CPC分类号： C07D217/26 ,  C07D211/36

摘要： &bgr;-alanine compounds or a pharmaceutically acceptable salt thereof, which is useful as a glycoprotein IIB/IIIa antagonist, inhibitor of blood platelet aggregation and inhibitor of the binding of fibrinogen to blood platelet; a composition containing the same, a process for the preparation of the compound, and a process for the treatment of diseases caused by thrombus formation, for example, are provided.

摘要翻译： β-丙氨酸化合物或其药学上可接受的盐，其可用作糖蛋白IIB / IIIa拮抗剂，血小板聚集抑制剂和纤维蛋白原与血小板结合的抑制剂; 提供含有该化合物的组合物，制备该化合物的方法，以及用于治疗由血栓形成引起的疾病的方法。

公开(公告)号：US07879844B2

公开(公告)日：2011-02-01

申请号：US12065234

申请日：2006-12-25

申请人： Takayuki Inoue ,  Akira Tanaka ,  Kazuo Nakai ,  Hiroshi Sasaki ,  Fumie Takahashi ,  Shohei Shirakami ,  Keiko Hatanaka ,  Yutaka Nakajima ,  Koichiro Mukoyoshi ,  Hisao Hamaguchi ,  Shigeki Kunikawa ,  Yasuyuki Higashi

发明人： Takayuki Inoue ,  Akira Tanaka ,  Kazuo Nakai ,  Hiroshi Sasaki ,  Fumie Takahashi ,  Shohei Shirakami ,  Keiko Hatanaka ,  Yutaka Nakajima ,  Koichiro Mukoyoshi ,  Hisao Hamaguchi ,  Shigeki Kunikawa ,  Yasuyuki Higashi

IPC分类号： A61K31/437 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  C07D471/04 ,  C07D471/14 ,  A61P37/00 ,  A61P25/28 ,  A61P35/00

CPC分类号： C07D451/04 ,  C07D471/04 ,  C07D471/14 ,  C07D519/00

摘要： The present invention provides a compound of formula (I) having an excellent JAK3 inhibition activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases inflammatory diseases, and allergic diseases. The compound according to the present invention has an inhibition activity against JAK3 and is thus useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transmission (e.g., rejection during organ/tissue transplantation, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, atopic dermatitis, Alzheimer's disease, and atherosclerotic disease), or diseases caused by abnormal cytokine signal transmission (e.g., cancer and leukemia).

摘要翻译： 本发明提供了具有优异的JAK3抑制活性的式（I）化合物，并且可用作治疗和/或预防各种免疫疾病，包括自身免疫性疾病炎性疾病和过敏性疾病的药剂的活性成分。 根据本发明的化合物对JAK3具有抑制活性，因此可用作治疗或预防由不良细胞因子信号传导引起的疾病（例如器官/组织移植期间的排斥，自身免疫性疾病，多发性硬化症）的活性成分 ，类风湿性关节炎，牛皮癣，哮喘，特应性皮炎，阿尔茨海默病和动脉粥样硬化疾病）或由异常细胞因子信号传导引起的疾病（例如癌症和白血病）。

公开(公告)号：US20100216798A1

公开(公告)日：2010-08-26

申请号：US11993229

申请日：2006-07-27

申请人： Kazuo Nakai ,  Fumie Takahashi ,  Kazuya Fujita ,  Yoshihiro Kozuki ,  Koichiro Mukoyoshi ,  Masamichi Inami ,  Norio Asai

发明人： Kazuo Nakai ,  Fumie Takahashi ,  Kazuya Fujita ,  Yoshihiro Kozuki ,  Koichiro Mukoyoshi ,  Masamichi Inami ,  Norio Asai

IPC分类号： A61K31/5025 ,  C07D487/04 ,  A61K31/519 ,  A61P37/00 ,  A61P11/06 ,  A61P37/06

CPC分类号： C07D487/04

摘要： There is provided fused heterocycles of imidazopyridazine or pyrazolopyrimidine derivative represented by the formula (I), which have excellent Lck inhibitory activity and are useful for a medicament particularly an immunosuppressive agent. [wherein one of Y and Z is C atom, and the other is N atom; —X— is —N(R1)— or the like, —R1 represents hydrogen or the like, -A- represents bond or the like, —R2 is cycloalkyl, aryl or the like, -E- is bond or the like, —R3 is aryl, aromatic heterocycle or the like, —R4, —R5 and —R6 are the same or different, each being hydrogen or the like.]

摘要翻译： 提供由式（I）表示的咪唑并哒嗪或吡唑并嘧啶衍生物的稠合杂环，其具有优异的Lck抑制活性，并且可用于药物，特别是免疫抑制剂。 [其中Y和Z之一是C原子，另一个是N原子; -X-是-N（R 1） - 等，-R 1表示氢等，-A-表示键等，-R 2是环烷基，芳基等，-E-是键等， -R3是芳基，芳香族杂环等，-R4，-R5和-R6相同或不同，各自为氢等。

公开(公告)号：US06770667B1

公开(公告)日：2004-08-03

申请号：US10088088

申请日：2002-03-21

申请人： Kiyotaka Ito ,  Glen W. Spears ,  Fumie Takahashi ,  Akira Yamada ,  Masaki Tomishima ,  Hiroshi Miyake

发明人： Kiyotaka Ito ,  Glen W. Spears ,  Fumie Takahashi ,  Akira Yamada ,  Masaki Tomishima ,  Hiroshi Miyake

IPC分类号： C07D23364

CPC分类号： C07D213/40 ,  C07D231/12 ,  C07D233/56 ,  C07D233/64 ,  C07D237/08 ,  C07D239/26 ,  C07D241/12 ,  C07D249/08 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

摘要： The present invention is a compound and pharmaceutical composition comprising a compound of formula (I): wherein R1 is a 4-(lower) alkyl-imidazol-1-yl or a 4,5-di(lower) alkyl-imidazol-1-yl group, R2 is a hydrogen atom or a lower alkyl group, and R3 is a fluorenyl group. The compound of formula (I) includes pharmaceutically acceptable salts: The compound of formula (I) and salts thereof have 5-HT antagonism activity.

摘要翻译： 本发明是包含式（I）化合物的化合物和药物组合物：其中R 1是4-（低级）烷基 - 咪唑-1-基或4,5-二（低级）烷基 - 咪唑 -1-基，R 2为氢原子或低级烷基，R 3为芴基。 式（I）化合物包括药学上可接受的盐：式（I）化合物及其盐具有5-HT拮抗活性。

公开(公告)号：US08163767B2

公开(公告)日：2012-04-24

申请号：US11995445

申请日：2006-07-13

申请人： Takayuki Inoue ,  Takashi Tojo ,  Masataka Morita ,  Yutaka Nakajima ,  Keiko Hatanaka ,  Shohei Shirakami ,  Hiroshi Sasaki ,  Akira Tanaka ,  Fumie Takahashi ,  Koichiro Mukoyoshi ,  Yasuyuki Higashi ,  Akira Okimoto ,  Takeshi Hondo ,  Hitoshi Sawada

发明人： Takayuki Inoue ,  Takashi Tojo ,  Masataka Morita ,  Yutaka Nakajima ,  Keiko Hatanaka ,  Shohei Shirakami ,  Hiroshi Sasaki ,  Akira Tanaka ,  Fumie Takahashi ,  Koichiro Mukoyoshi ,  Yasuyuki Higashi ,  Akira Okimoto ,  Takeshi Hondo ,  Hitoshi Sawada

IPC分类号： A61K31/44 ,  C07D471/14

CPC分类号： C07D471/14 ,  C07D519/00

摘要： The invention relates to compound of the formula (I) or its salt, wherein —R1, —R2, —R3, —R4, —R5, -M-, —X— and —Y═ are as defined in the description, their use of as, medicament, the process for their preparation and use for the treatment of JAK3 mediated diseases.

摘要翻译： 本发明涉及式（I）化合物或其盐，其中-R1，-R2，-R3，-R4，-R5，-M-，-X-和-Y =如说明书中所定义，它们 使用as，药物，其制备方法和用于治疗JAK3介导的疾病。

公开(公告)号：US06380215B1

公开(公告)日：2002-04-30

申请号：US08495572

申请日：1995-08-04

申请人： Mitsuru Ohkubo ,  Fumie Takahashi ,  Toshio Yamanaka ,  Hiroyoshi Sakai ,  Masayuki Kato

发明人： Mitsuru Ohkubo ,  Fumie Takahashi ,  Toshio Yamanaka ,  Hiroyoshi Sakai ,  Masayuki Kato

IPC分类号： A61K314545

CPC分类号： C07D401/06 ,  C07D211/56 ,  C07D211/60 ,  C07D405/14 ,  C07D413/06 ,  Y02P20/55

摘要： This invention relates to &bgr;-alanine derivatives represented by the following formula: wherein each symbol is as defined in the specification and pharmaceutically acceptable salt thereof which is glycoprotein IIb/IIIa antagonist, inhibitor of blood platelets aggregation and inhibitor of the binding of fibrinogen to blood platelets, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment diseases indicated in the specification to a human being or an animal.

摘要翻译： 本发明涉及由下式表示的β-丙氨酸衍生物：其中每个符号如说明书中所定义，其药学上可接受的盐是糖蛋白IIb / IIIa拮抗剂，血小板聚集抑制剂和纤维蛋白原与血液结合的抑制剂 血小板，其制备方法，包含其的药物组合物以及用于预防和/或治疗本说明书中针对人或动物的疾病的方法。