公开(公告)号：US08575153B2

公开(公告)日：2013-11-05

申请号：US13131561

申请日：2009-11-27

申请人： Takahiro Kitamura ,  Hajime Yamada ,  Shunji Takemura ,  Masanori Ashikawa ,  Tetsuya Ishikawa ,  Yoshiharu Miyake ,  Akiyasu Kouketsu ,  Seiichi Sato ,  Hiroyuki Ishiwata ,  Yuichiro Tabunoki ,  Manabu Shibasaki ,  Takatoshi Ozawa ,  Ryota Shigemi ,  Takeshi Doi ,  Masahiro Tamura

发明人： Takahiro Kitamura ,  Hajime Yamada ,  Shunji Takemura ,  Masanori Ashikawa ,  Tetsuya Ishikawa ,  Yoshiharu Miyake ,  Akiyasu Kouketsu ,  Seiichi Sato ,  Hiroyuki Ishiwata ,  Yuichiro Tabunoki ,  Manabu Shibasaki ,  Takatoshi Ozawa ,  Ryota Shigemi ,  Takeshi Doi ,  Masahiro Tamura

IPC分类号： A61K31/506 ,  C07D239/48

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

摘要： To provide a novel JAK3 inhibitor that is useful as a preventive and/or therapeutic agent for rejection and graft versus host disease (GvHD) in organ transplantation, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Sjögren syndrome, Behcet's disease, type I diabetes mellitus, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, ulcerative colitis, Crohn's disease, asthma, allergic rhinitis, atopic dermatitis, contact dermatitis, urticaria, eczema, psoriasis, allergic conjunctivitis, uveitis, cancer, leukemia and the like. The pyridine-3-carboxyamide derivative represented by the general formula (1): or its salt or a solvate thereof.

摘要翻译： 提供可用作器官移植，类风湿关节炎，多发性硬化症，系统性红斑狼疮，Sjögren综合征，Behcet氏病，I型糖尿病的排斥反应和宿主疾病（GvHD）的预防和/或治疗剂的新型JAK3抑制剂 过敏性甲状腺炎，特发性血小板减少性紫癜，溃疡性结肠炎，克罗恩病，哮喘，过敏性鼻炎，特应性皮炎，接触性皮炎，荨麻疹，湿疹，牛皮癣，过敏性结膜炎，葡萄膜炎，癌症，白血病等。 由通式（1）表示的吡啶-3-甲酰胺衍生物或其盐或其溶剂化物。

公开(公告)号：US20110237590A1

公开(公告)日：2011-09-29

申请号：US13131561

申请日：2009-11-27

申请人： Takahiro Kitamura ,  Hajime Yamada ,  Shunji Takemura ,  Masanori Ashikawa ,  Tetsuya Ishikawa ,  Yoshiharu Miyake ,  Akiyasu Kouketsu ,  Seiichi Sato ,  Hiroyuki Ishiwata ,  Yuichiro Tabunoki ,  Manabu Shibasaki ,  Takatoshi Ozawa ,  Ryota Shigemi ,  Takeshi Doi ,  Masahiro Tamura

发明人： Takahiro Kitamura ,  Hajime Yamada ,  Shunji Takemura ,  Masanori Ashikawa ,  Tetsuya Ishikawa ,  Yoshiharu Miyake ,  Akiyasu Kouketsu ,  Seiichi Sato ,  Hiroyuki Ishiwata ,  Yuichiro Tabunoki ,  Manabu Shibasaki ,  Takatoshi Ozawa ,  Ryota Shigemi ,  Takeshi Doi ,  Masahiro Tamura

IPC分类号： A61K31/5377 ,  C07D213/74 ,  C07D401/12 ,  C07D413/12 ,  C07D211/46 ,  A61K31/44 ,  A61K31/497 ,  A61K31/4545 ,  A61P37/02 ,  A61P37/06

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

摘要： To provide a novel JAK3 inhibitor that is useful as a preventive and/or therapeutic agent for rejection and graft versus host disease (GvHD) in organ transplantation, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Sjögren syndrome, Behcet's disease, type I diabetes mellitus, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, ulcerative colitis, Crohn's disease, asthma, allergic rhinitis, atopic dermatitis, contact dermatitis, urticaria, eczema, psoriasis, allergic conjunctivitis, uveitis, cancer, leukemia and the like. The pyridine-3-carboxyamide derivative represented by the general formula (1): or its salt or a solvate thereof.

摘要翻译： 提供可用作器官移植，类风湿关节炎，多发性硬化症，系统性红斑狼疮，Sjögren综合征，Behcet氏病，I型糖尿病的排斥反应和宿主疾病（GvHD）的预防和/或治疗剂的新型JAK3抑制剂 过敏性甲状腺炎，特发性血小板减少性紫癜，溃疡性结肠炎，克罗恩病，哮喘，过敏性鼻炎，特应性皮炎，接触性皮炎，荨麻疹，湿疹，牛皮癣，过敏性结膜炎，葡萄膜炎，癌症，白血病等。 由通式（1）表示的吡啶-3-甲酰胺衍生物或其盐或其溶剂合物。

公开(公告)号：US20120004197A1

公开(公告)日：2012-01-05

申请号：US13256549

申请日：2010-03-31

申请人： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

发明人： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

IPC分类号： A61K31/4706 ,  C07D413/12 ,  C07D215/14 ,  C07D215/233 ,  C07D401/12 ,  A61P7/06 ,  C07D413/14 ,  A61K31/5377 ,  A61K31/47 ,  A61K31/496 ,  A61K31/69 ,  C07D215/44 ,  C07F5/02

CPC分类号： C07D215/42 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/69 ,  C07D215/233 ,  C07D215/44 ,  C07D215/46 ,  C07D215/48 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12

摘要： Disclosed is a compound which has a low molecular weight and has an activity of enhancing the production of EPO and/or an activity of enhancing the production of hemoglobin. Specifically disclosed is and EPO production enhancer and/or a hemoglobin production enhancer comprising a 1-acyl-4-(substituted oxy, substituted amino, or substituted thio)-1,2,3,4-tetrahydroquinoline derivative, more specifically a tetrahydroquinoline compound represented by general formula (1) [wherein R1, R2, R2′, R3 and R3′ independently represent a hydrogen atom, a C1-6 alkyl group, or the like; R4, R5, R6, R7, R8, R9 and R10 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or the like; A represents N—R11, a sulfur atom, or an oxygen atom; R11 represents a hydrogen atom, a C1-6 alkyl group, or the like; B represents a C6-14 aryl group, or a 5- to 10-membered heterocyclic group; and n represents an integer of 0 or 1], a salt of the tetrahydroquinoline compound, or a solvate of the tetrahydroquinoline compound or the salt.

摘要翻译： 公开了具有低分子量且具有增强EPO产生活性和/或提高血红蛋白生成活性的化合物。 具体公开的是EPO生产增强剂和/或包含1-酰基-4-（取代的氧基，取代的氨基或取代的硫代）-1,2,3,4-四氢喹啉衍生物，更具体地是四氢喹啉化合物的血红蛋白生成增强剂 由通式（1）表示[其中R1，R2，R2'，R3和R3'独立地表示氢原子，C1-6烷基等; R 4，R 5，R 6，R 7，R 8，R 9和R 10独立地表示氢原子，卤素原子，C 1-6烷基等; A表示N-R11，硫原子或氧原子; R 11表示氢原子，C 1-6烷基等; B表示C 6-14芳基或5至10元杂环基; n表示0或1的整数]，四氢喹啉化合物的盐或四氢喹啉化合物或其盐的溶剂合物。

公开(公告)号：US08791090B2

公开(公告)日：2014-07-29

申请号：US13256549

申请日：2010-03-31

申请人： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

发明人： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

IPC分类号： A01N57/00 ,  A61K31/385

CPC分类号： C07D215/42 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/69 ,  C07D215/233 ,  C07D215/44 ,  C07D215/46 ,  C07D215/48 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12

摘要： Disclosed is a compound which has a low molecular weight and has an activity of enhancing the production of EPO and/or an activity of enhancing the production of hemoglobin. Specifically disclosed is and EPO production enhancer and/or a hemoglobin production enhancer comprising a 1-acyl-4-(substituted oxy, substituted amino, or substituted thio)-1,2,3,4-tetrahydroquinoline derivative, more specifically a tetrahydroquinoline compound represented by general formula (1) [wherein R1, R2, R2′, R3 and R3′ independently represent a hydrogen atom, a C1-6 alkyl group, or the like; R4, R5, R6, R7, R8, R9 and R10 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or the like; A represents N—R11, a sulfur atom, or an oxygen atom; R11 represents a hydrogen atom, a C1-6 alkyl group, or the like; B represents a C6-14 aryl group, or a 5- to 10-membered heterocyclic group; and n represents an integer of 0 or 1], a salt of the tetrahydroquinoline compound, or a solvate of the tetrahydroquinoline compound or the salt.

摘要翻译： 公开了具有低分子量且具有增强EPO产生活性和/或提高血红蛋白生成活性的化合物。 具体公开的是EPO生产增强剂和/或包含1-酰基-4-（取代的氧基，取代的氨基或取代的硫代）-1,2,3,4-四氢喹啉衍生物，更具体地是四氢喹啉化合物的血红蛋白生成增强剂 由通式（1）表示[其中R1，R2，R2'，R3和R3'独立地表示氢原子，C1-6烷基等; R 4，R 5，R 6，R 7，R 8，R 9和R 10独立地表示氢原子，卤素原子，C 1-6烷基等; A表示N-R11，硫原子或氧原子; R 11表示氢原子，C 1-6烷基等; B表示C 6-14芳基或5至10元杂环基; n表示0或1的整数]，四氢喹啉化合物的盐或四氢喹啉化合物或其盐的溶剂合物。

公开(公告)号：US07087606B2

公开(公告)日：2006-08-08

申请号：US10960993

申请日：2004-10-12

申请人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

发明人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC分类号： A01N43/58 ,  A61K31/50

CPC分类号： C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  C07D237/24

摘要： Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represent a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represent a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to medicinal compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

摘要翻译： 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子 或烷基，羟基烷基，二羟基烷基或炔基或R 2和R 3可以与相邻的氮原子一起形成取代或未取代的含氮的 饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子等，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。

公开(公告)号：US20060142292A1

公开(公告)日：2006-06-29

申请号：US10544881

申请日：2004-03-16

申请人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

发明人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC分类号： A61K31/501 ,  C07D403/02 ,  A61K31/50

CPC分类号： A61K31/501 ,  A61K31/50 ,  C07D237/14

摘要： A phenylpyridazine derivative represented by the formula (1): Wherein, R1, R2, R3, X, Y, Z and n have the same meaning as defined in the specification; or a salt thereof, or a medicine containing the compound. The present invention provides water-soluble phenylpyridazine derivatives and medicines containing them, which have excellent inhibitory activity against interleukin-β production, high water solubility and high oral absorbability.

摘要翻译： 由式（1）表示的苯基哒嗪衍生物：其中R1，R2，R3，X，Y，Z和n与说明书中定义相同; 或其盐，或含有该化合物的药物。 本发明提供水溶性苯基哒嗪衍生物和含有它们的药物，其对白细胞介素-β产生具有优异的抑制活性，高水溶性和高口服吸收性。

公开(公告)号：US07211577B2

公开(公告)日：2007-05-01

申请号：US10544881

申请日：2004-03-16

申请人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

发明人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC分类号： C07D237/04 ,  C07D403/06 ,  A61K31/50 ,  A61K31/51

CPC分类号： A61K31/501 ,  A61K31/50 ,  C07D237/14

摘要： A phenylpyridazine derivative represented by the formula (1): Wherein, R1, R2, R3, X, Y, Z and n have the same meaning as defined in the specification; or a salt thereof, or a medicine containing the compound. The present invention provides water-soluble phenylpyridazine derivatives and medicines containing them, which have excellent inhibitory activity against interleukin-β production, high water solubility and high oral absorbability.

摘要翻译： 由式（1）表示的苯基哒嗪衍生物：其中R1，R2，R3，X，Y，Z和n与说明书中定义相同; 或其盐，或含有该化合物的药物。 本发明提供水溶性苯基哒嗪衍生物和含有它们的药物，其对白细胞介素-β产生具有优异的抑制活性，高水溶性和高口服吸收性。

公开(公告)号：US06869954B2

公开(公告)日：2005-03-22

申请号：US10253523

申请日：2002-09-25

申请人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

发明人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC分类号： C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  A61P1/04 ,  A61P9/00 ,  A61P19/02 ,  A61P19/10 ,  A61P29/00 ,  A61P31/04 ,  A61P37/02 ,  A61P43/00 ,  C07D237/24 ,  A61K31/51 ,  C07D237/04 ,  C07D403/06

CPC分类号： C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  C07D237/24

摘要： Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represent a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represent a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to medicinal compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

摘要翻译： 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子或烷基，羟烷基，二羟基烷基或炔基，或R 2 >和R 3可以与相邻的氮原子一起形成取代或未取代的含氮饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子或 n，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。

公开(公告)号：US20050085480A1

公开(公告)日：2005-04-21

申请号：US10960993

申请日：2004-10-12

申请人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

发明人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC分类号： C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  A61P1/04 ,  A61P9/00 ,  A61P19/02 ,  A61P19/10 ,  A61P29/00 ,  A61P31/04 ,  A61P37/02 ,  A61P43/00 ,  C07D237/24 ,  C07D43/02

CPC分类号： C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  C07D237/24

摘要： Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represent a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represent a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to medicinal compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

摘要翻译： 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子 或烷基，羟基烷基，二羟基烷基或炔基或R 2和R 3可以与相邻的氮原子一起形成取代或未取代的含氮的 饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子等，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。

公开(公告)号：US06861428B2

公开(公告)日：2005-03-01

申请号：US10396726

申请日：2003-03-26

申请人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

发明人： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC分类号： A61K31/50 ,  A61K31/501 ,  C07D237/14 ,  C07D237/24 ,  A61K31/51 ,  C07D237/04 ,  C07D403/06

CPC分类号： A61K31/50 ,  A61K31/501 ,  C07D237/14 ,  C07D237/24

摘要： Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represents a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represents a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to pharmaceutical compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

摘要翻译： 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子或烷基，羟基烷基，二羟基烷基或炔基，或R 2 >和R 3可以与相邻的氮原子一起形成取代或未取代的含氮饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子或 n，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。