公开(公告)号：US20060160804A1

公开(公告)日：2006-07-20

申请号：US11385995

申请日：2006-03-22

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： A61K31/5377 ,  A61K31/501 ,  C07D413/02 ,  C07D403/02

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。

公开(公告)号：US06680316B1

公开(公告)日：2004-01-20

申请号：US09926040

申请日：2001-08-20

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Takayuki Matsuda ,  Kyoko Yasuoka ,  Tomoko Furuyama

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Takayuki Matsuda ,  Kyoko Yasuoka ,  Tomoko Furuyama

IPC分类号： C07D23724

CPC分类号： C07D237/24

摘要： Objects of the invention are to provide compounds having excellent activity against interleukin-1&bgr; production and also medicines comprising them as effective ingredients. Pyridazin-3-one derivatives represented by the following formula (1): wherein Ar1 represents a substituted or unsubstituted aromatic group, Ar2 represents a phenyl group having a substituent at least at the 4-position thereof, R1 represents a linear or branched alkyl group, an alkyl group having a cyclic structure, a substituted or unsubstituted phenyl group or a substituted or unsubstituted phenyl(lower alkyl) group, and R2 represents a cyano group, a carboxyl group, a (lower alkoxy)carbonyl group, a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted carbamoyl group, or salts thereof; and medicines comprising them as effective ingredients.

摘要翻译： 本发明的目的是提供对白细胞介素-1β生产具有优异活性的化合物以及包含它们作为有效成分的药物。由下式（1）表示的哒嗪-3-酮衍生物：其中Ar 1表示取代或未取代的 芳基，Ar 2表示至少在其4位具有取代基的苯基，R 1表示直链或支链烷基，具有环状结构的烷基，取代或未取代的苯基或 取代或未取代的苯基（低级烷基），R 2表示氰基，羧基，（低级烷氧基）羰基，取代或未取代的低级烷基或取代或未取代的氨基甲酰基，或盐 的; 和包含它们作为有效成分的药物。

公开(公告)号：US06403586B1

公开(公告)日：2002-06-11

申请号：US09622897

申请日：2000-08-31

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Takayuki Matsuda ,  Soichi Oda ,  Yuriko Habata ,  Kyoko Kotaki

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Takayuki Matsuda ,  Soichi Oda ,  Yuriko Habata ,  Kyoko Kotaki

IPC分类号： A61K3150

CPC分类号： C07D401/06 ,  C07D237/02 ,  C07D237/04 ,  C07D237/22 ,  C07D237/24 ,  C07D401/12

摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a lower alkoxyl group, a lower alkylthio group or a halogen atom; R2 represents H, a lower alkoxyl group, a lower alkylthio group or a halogen atom; R3 represents a lower alkyl or lower alkenyl group, which may be substituted by one or more OHs, CNs, lower cycloalkyl groups, (substituted) aromatic groups or (substituted) carbamoyl groups; R4 represents COOH, a lower alkoxycarbonyl group, a (substituted) carbamoyl group, a (substituted) amino group, or a (substituted) ureido group; 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-1&bgr; 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R1表示低级烷氧基，低级烷硫基或卤素原子; R2表示H，低级烷氧基，低级烷硫基或卤素原子; R 3表示低级烷基或低级烯基，其可以被一个或多个OH，CN，低级环烷基，（取代的）芳族基团或（取代的）氨基甲酰基取代; R4表示COOH，低级烷氧基羰基，（取代）氨基甲酰基，（取代）氨基或（取代）脲基; 虚线表示4位和5位之间的碳 - 碳键为单键或双键，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。

公开(公告)号：US06348468B1

公开(公告)日：2002-02-19

申请号：US09530949

申请日：2000-05-15

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： A61K31501

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-1&bgr; 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R1表示（取代的）芳基，R2表示通过低级烷氧基或低级烷硫基在4位被取代的苯基，R3表示低级烷氧基 基团，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 - 碳键为单键或双键 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。

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。

公开(公告)号：US07314877B2

公开(公告)日：2008-01-01

申请号：US10547779

申请日：2004-03-03

申请人： Seiichi Sato ,  Tomoyuki Koshi ,  Toshimi Mizoguchi ,  Kyoko Yasuoka ,  Natsuyo Kumai ,  Junko Totsuka ,  Masahiro Tamura ,  Masao Ohkuchi

发明人： Seiichi Sato ,  Tomoyuki Koshi ,  Toshimi Mizoguchi ,  Kyoko Yasuoka ,  Natsuyo Kumai ,  Junko Totsuka ,  Masahiro Tamura ,  Masao Ohkuchi

IPC分类号： C07D405/04 ,  A61K31/501

CPC分类号： C07D405/04

摘要： The present invention is directed to a compound represented by formula (1): (wherein R1 represents an alkyl group which may have a substituent or an alkenyl group which may have a substituent; and each of R2 and R3 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, a dihydroxyalkyl group, or an alkynyl group, or R2 and R3 form, together with the nitrogen atom adjacent thereto, a nitrogen-containing saturated heterocyclic group which may have a substituent) and a drug composition containing the compound. The compound exhibits tumor necrosis factor (TNF-α) production inhibitory effect and improved absorption upon oral administration.

摘要翻译： 本发明涉及由式（1）表示的化合物：其中R 1表示可以具有取代基的烷基或可具有取代基的烯基; R 1， SO 2和R 3表示氢原子，烷基，羟基烷基，二羟基烷基或炔基，或R 2和 R 3形式与与其相邻的氮原子，可以具有取代基的含氮饱和杂环基）和含有该化合物的药物组合物。 该化合物表现出肿瘤坏死因子（TNF-α）产生抑制作用和口服给药改善吸收。

公开(公告)号：US20060189621A1

公开(公告)日：2006-08-24

申请号：US10547779

申请日：2004-03-03

申请人： Seiichi Sato ,  Tomoyuki Koshi ,  Toshimi Mizoguchi ,  Kyoko Yasuoka ,  Junko Totsuka ,  Masahiro Tamura ,  Masao Ohkuchi

发明人： Seiichi Sato ,  Tomoyuki Koshi ,  Toshimi Mizoguchi ,  Kyoko Yasuoka ,  Junko Totsuka ,  Masahiro Tamura ,  Masao Ohkuchi

IPC分类号： A61K31/501 ,  C07D405/02

CPC分类号： C07D405/04

摘要： The present invention is directed to a compound represented by formula (1): (wherein R1 represents an alkyl group which may have a substituent or an alkenyl group which may have a substituent; and each of R2 and R3 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, a dihydroxyalkyl group, or an alkynyl group, or R2 and R3 form, together with the nitrogen atom adjacent thereto, a nitrogen-containing saturated heterocyclic group which may have a substituent) and a drug composition containing the compound. The compound exhibits tumor necrosis factor (TNF-α) production inhibitory effect and improved absorption upon oral administration.

摘要翻译： 本发明涉及由式（1）表示的化合物：其中R 1表示可以具有取代基的烷基或可具有取代基的烯基; R 1， SO 2和R 3表示氢原子，烷基，羟基烷基，二羟基烷基或炔基，或R 2和 R 3形式与与其相邻的氮原子，可以具有取代基的含氮饱和杂环基）和含有该化合物的药物组合物。 该化合物表现出肿瘤坏死因子（TNF-α）产生抑制作用和口服给药改善吸收。

公开(公告)号：US06664256B1

公开(公告)日：2003-12-16

申请号：US09612953

申请日：2000-07-10

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Natsuyo Kumai ,  Kyoko Kotaki

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Natsuyo Kumai ,  Kyoko Kotaki

IPC分类号： A61K3150

CPC分类号： C07D401/12 ,  A61K31/50 ,  C07D237/08 ,  C07D237/12 ,  C07D237/14 ,  C07D237/18 ,  C07D237/20 ,  C07D237/24 ,  C07D405/04 ,  C07D417/04

摘要： Phenylpyridazine compounds represented by the following formula (I): are provided, wherein R1, R2, R3, R4, and n are as defined herein having excellent inhibitory activity against interleukin-1&bgr; production, and useful in the treatment of prevention of diseases caused by stimulation of interleukin-1&bgr; production, such as immune system diseases, inflammatory diseases, and ischemic diseases.

摘要翻译： 提供由下式（I）表示的苯基哒嗪化合物：其中R 1，R 2，R 3，R 4和n如本文所定义，对白细胞介素-1β生产具有优异的抑制活性 可用于治疗由免疫系统疾病，炎症性疾病和缺血性疾病等白细胞介素-1β产生刺激引起的疾病的预防。

公开(公告)号：US5354664A

公开(公告)日：1994-10-11

申请号：US110011

申请日：1993-08-23

申请人： Takeshi Doi ,  Akio Iwasaki ,  Yushi Saino ,  Shigeru Kimura ,  Masao Ohkuchi

发明人： Takeshi Doi ,  Akio Iwasaki ,  Yushi Saino ,  Shigeru Kimura ,  Masao Ohkuchi

IPC分类号： A61K38/00 ,  C07K14/745 ,  C12N15/12 ,  C12N15/15 ,  C12N5/10

CPC分类号： C07K14/7455 ,  A61K38/00

摘要： Thrombin-binding substances capable of promoting anti-thrombin III activity and inhibiting platelet aggregation, and by themselves possessing anti-thrombin activity are disclosed. The thrombin-binding substances are useful as an effective component of anticoagulant agents, and can be produced inexpensively on a large scale.

摘要翻译： 公开了能够促进抗凝血酶III活性和抑制血小板聚集的本身具有抗凝血酶活性的凝血酶结合物质。 凝血酶结合物质作为抗凝血剂的有效成分是有用的，可以大量生产成本低廉。