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1. 发明申请

US20070208025A1 NOVEL PYRIDAZINE DERIVATIVES AND MEDICINES CONTAINING THE SAME AS EFFECTIVE INGREDIENTS 审中-公开
标题翻译：新的吡咯烷酮衍生物和含有相同成分的药物
公开(公告)号：US20070208025A1
公开(公告)日：2007-09-06
申请号：US11741947
申请日：2007-04-30
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/50
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代）芳基，取代的芳氧基，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

2. 发明授权

US07211577B2 Water-soluble phenylpyridazine derivative and medicine containing the same 失效
标题翻译：水溶性苯基哒嗪衍生物及含有它的药物
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。

3. 发明申请

US20050267113A1 Novel pyridazine derivatives and medicines containing the same as effective ingredients 审中-公开
标题翻译：新颖的哒嗪衍生物和含有与有效成分相同的药物
公开(公告)号：US20050267113A1
公开(公告)日：2005-12-01
申请号：US11203174
申请日：2005-08-15
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/50 , A61K31/501 , A61P19/02 , A61P19/10 , A61P29/00 , A61P37/00 , C07D213/00 , C07D237/00 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/04 , C07D401/06 , C07D43/02
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immmune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位取代的苯基通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4位和5位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生成具有优异的抑制活性，并且可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

4. 发明申请

US20080119474A1 NOVEL PYRIDAZINE DERIVATIVES AND MEDICINES CONTAINING THE SAME AS EFFECTIVE INGREDIENTS 审中-公开
标题翻译：新的吡咯烷酮衍生物和含有相同成分的药物
公开(公告)号：US20080119474A1
公开(公告)日：2008-05-22
申请号：US12013691
申请日：2008-01-14
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/50 , C07D237/02 , A61P19/00 , A61P9/00 , A61P37/00
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代）芳基，取代的芳氧基，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β产生具有优异的抑制活性，并且可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防和治疗。

5. 发明申请

US20050085480A1 Water-soluble phenylpyridazine compounds and compositions containing the same 失效
标题翻译：水溶性苯基哒嗪化合物及其组合物
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。

6. 发明授权

US4505893A Purified plasminogen activator, process for its production and thrombolytic composition containing it 失效
标题翻译：纯化的纤溶酶原激活剂，其生产过程及含有溶血栓组合物
公开(公告)号：US4505893A
公开(公告)日：1985-03-19
申请号：US519347
申请日：1983-08-01
申请人： Toshihito Mori , Hideo Yoshizaki , Akio Hasegawa
发明人： Toshihito Mori , Hideo Yoshizaki , Akio Hasegawa
IPC分类号： C12N9/64 , A61K38/00 , A61K38/46 , A61K38/48 , A61P7/02 , C12N5/02 , C12N9/72 , C12R1/91 , A61K37/48 , C12P21/00
CPC分类号： C12N9/6456 , A61K38/00
摘要： A plasminogen activator obtained from a tissue cultured liquor of human normal tissue derived cells, e.g., human embryonic derived cells, human placenta derived cells etc., and having the following properties:(a) molecular weight measured by gel filtration: 63,000.+-.10,000,(b) isoelectric point: 7.0-8.5,(c) affinity to fibrin: present,(d) affinity to concanavalin A: present,(e) optimum pH: 7-9.5, and(f) stability: does not lose activity at 60.degree. C. for 10 hours but loses about 5% of activity at pH 2-3 at 98.degree. C. for a minute; a process for the production of the aforesaid plasminogen activator; and a thrombolytic composition containing the aforesaid plasminogen activator as an active ingredient are disclosed.
摘要翻译：从人正常组织衍生细胞（例如人胚胎衍生细胞，人胎盘衍生细胞等）的组织培养液中获得并具有以下性质的纤溶酶原激活剂：（a）通过凝胶过滤测量的分子量：63,000 +/- 10,000，（b）等电点：7.0-8.5，（c）对纤维蛋白的亲和力：存在，（d）对伴刀豆球蛋白的亲和力A：存在，（e）最适pH：7-9.5和（f）稳定性：不失去在60℃下活化10小时，但在98℃在pH 2-3下失去约5％的活性一分钟; 一种生产上述纤溶酶原激活物的方法; 并且公开了含有上述纤溶酶原激活剂作为活性成分的血栓溶解组合物。

7. 发明授权

US07087606B2 Water-soluble phenylpyridazine compounds and compositions containing the same 失效
标题翻译：水溶性苯基哒嗪化合物及其组合物
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。

8. 发明申请

US20060142292A1 Water-soluble phenylpyridazine derivative and medicine containing the same 失效
标题翻译：水溶性苯基哒嗪衍生物及含有它的药物
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。

9. 发明申请

US20050065155A1 Novel pyridazine derivatives and medicines containing the same as effective ingredients 审中-公开
标题翻译：新颖的哒嗪衍生物和含有与有效成分相同的药物
公开(公告)号：US20050065155A1
公开(公告)日：2005-03-24
申请号：US10986350
申请日：2004-11-12
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/50 , A61K31/501 , A61P19/02 , A61P19/10 , A61P29/00 , A61P37/00 , C07D213/00 , C07D237/00 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/04 , C07D401/06 , C07D43/02
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4-位被低级烷氧基或低级烷硫基取代的苯基 R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代的）含氮杂环残基，（取代的））氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5位之间的碳 - 碳键 - 位是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

10. 发明授权

US4873222A Placenta-derived anticoagulating substance 失效
标题翻译：胎盘衍生抗凝物质
公开(公告)号：US4873222A
公开(公告)日：1989-10-10
申请号：US103686
申请日：1987-10-02
申请人： Koichi Arai , Hideo Yoshizaki
发明人： Koichi Arai , Hideo Yoshizaki
IPC分类号： A61K35/50 , A61K38/00 , A61P7/02 , C07K1/14 , C07K1/22 , C07K14/435 , C07K14/745
CPC分类号： A61K35/50
摘要： A human placenta-derived antiocoagulating substance is prepared by homogenizing a human plancenta, subjecting the resulting homogenate to centrifugal separation, extracting the thus-obtained sediment with a chelating agent, and then separating and purifying the extract. The substance has a molecular weight of 73,000.+-.2,000 as measured in reduced and non-reduced states by SDS-polyacrylamide gel electrophoresis. Its isoelectric point ranges from 6.2 to 6.6 as measured by isoelectric column electrophoresis using an ampholyte. It is inactivated by a heat treatment at 50.degree. C. for 30 minutes, is stable in a pH range of 5.5-8.5 (37.degree. C.) and is also stable in plasma at 37.degree. C. for 15 minutes. It can prolong the recalcification time, prothrombin time and activated partial thromboplastic time.
摘要翻译：人胎盘来源的抗凝血物质是通过将人平均匀化，将得到的匀浆进行离心分离，用螯合剂萃取由此获得的沉淀物，然后分离和纯化提取物来制备的。该物质通过SDS-聚丙烯酰胺凝胶电泳在还原和非还原状态下测得的分子量为73,000 +/- 2,000。其等电点在6.2至6.6之间，通过使用两性电解质的等电泳柱电泳测量。通过在50℃下热处理30分钟而灭活，在5.5-8.5（37℃）的pH范围内是稳定的，并且在37℃等离子体中也稳定15分钟。可延长再钙化时间，凝血酶原时间和活化部分血栓形成时间。

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