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1. 发明授权

US06861428B2 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：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。

2. 发明授权

US08268789B2 PAR-2 antagonists 失效
标题翻译： PAR-2拮抗剂
公开(公告)号：US08268789B2
公开(公告)日：2012-09-18
申请号：US11576304
申请日：2005-09-30
申请人： Mototsugu Kabeya , Kyoko Yasuoka , Toru Kanke , Hiroyuki Ishiwata , Junya Tagashira
发明人： Mototsugu Kabeya , Kyoko Yasuoka , Toru Kanke , Hiroyuki Ishiwata , Junya Tagashira
IPC分类号： A61K38/06 , A61K38/02
CPC分类号： C07K5/0827 , A61K38/00 , C07D209/14 , C07K5/0806 , C07K5/0812
摘要： Compounds represented by the general formula (1) or salts thereof or solvates of both; PAR-2 antagonists containing the compounds; and preventive or therapeutic agents for PAR-2 related diseases containing the antagonists as the active ingredient: (1) wherein R1 is hydrogen, halogeno, or a group represented by the general formula (2): (wherein R11 is straight-chain or branched C1-6 alkylene or the like; and R12 and R13 together with the nitrogen atom adjacent to them form a 5- to 7-membered ring); R2 is straight-chain or branched C1-6 alkyl or the like; R3 and R4 are each independently hydrogen, one to three halogen atoms, or the like; and A1-A2-A3 is a tripeptide residue composed of α-amino acids each independently selected from the group consisting of glycine, alanine, cyclohexylalanine, and so on.
摘要翻译：由通式（1）表示的化合物或其盐或两者的溶剂合物; 含有这些化合物的PAR-2拮抗剂; 以及含有拮抗剂作为活性成分的PAR-2相关疾病的预防或治疗剂：（1）其中R1是氢，卤素或由通式（2）表示的基团：（其中R11是直链或支链的 C 1-6亚烷基等; R 12和R 13与它们相邻的氮原子一起形成5-至7-元环）; R2是直链或支链C 1-6烷基等; R3和R4各自独立地为氢，一至三个卤素原子等; A1-A2-A3是由各自独立地选自甘氨酸，丙氨酸，环己基丙氨酸等的α-氨基酸组成的三肽残基。

3. 发明申请

US20090012263A1 Process for Production of (1,3-Disubstituted Indolyl)-Urea Derivatives, Intermediates Therefor, and Process for Production of the Intermediates 审中-公开
标题翻译：（1,3-二取代吲哚基） - 脲衍生物的制备方法，其中间体及其制备方法
公开(公告)号：US20090012263A1
公开(公告)日：2009-01-08
申请号：US11576311
申请日：2005-09-30
申请人： Mototsugu Kabeya , Kyoko Yasuoka
发明人： Mototsugu Kabeya , Kyoko Yasuoka
IPC分类号： C07K5/083 , C07D209/04
CPC分类号： C07K5/0827 , A61K38/00 , C07D209/14 , C07K5/0806 , C07K5/0812
摘要： A process for the production of (1,3-disubstituted indolyl) urea derivatives represented by the general formula (1), characterized by reacting a 1-substituted-aminoindole derivative with a phenyl halocarbonate to form a carbamate derivative, subjecting the carbamate derivative to Mannich reaction with a secondary amine and formaldehyde to form a 3-aminomethylindole derivative represented by the general formula (6), and then reacting the derivative (6) with a peptide derivative; indole derivatives represented by the general formula (6) which are intermediates for the above process; and a process for the production of the indole derivatives.
摘要翻译：一种制备由通式（1）表示的（1,3-二取代的吲哚基）脲衍生物的方法，其特征在于使1-取代的 - 氨基吲哚衍生物与卤代碳酸苯酯反应形成氨基甲酸酯衍生物，使氨基甲酸酯衍生物曼尼希与仲胺和甲醛反应形成由通式（6）表示的3-氨基甲基吲哚衍生物，然后使衍生物（6）与肽衍生物反应; 由通式（6）表示的作为上述方法的中间体的吲哚衍生物; 以及生产吲哚衍生物的方法。

4. 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。

5. 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。

6. 发明授权

US07314877B2 Benzofuran derivative 失效
标题翻译：苯并呋喃衍生物
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。

7. 发明申请

US20060189621A1 Benzofuran derivative 失效
标题翻译：苯并呋喃衍生物
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。

8. 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。

9. 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。

10. 发明申请

US20090012006A1 Par-2 Antagonists 失效
标题翻译： Par-2拮抗剂
公开(公告)号：US20090012006A1
公开(公告)日：2009-01-08
申请号：US11576304
申请日：2005-09-30
申请人： Mototsugu Kabeya , Kyoko Yasuoka , Toru Kanke , Hiroyuki Ishiwata , Junya Tagashira
发明人： Mototsugu Kabeya , Kyoko Yasuoka , Toru Kanke , Hiroyuki Ishiwata , Junya Tagashira
IPC分类号： A61K38/06 , C07K5/083 , A61P35/00 , A61P11/06
CPC分类号： C07K5/0827 , A61K38/00 , C07D209/14 , C07K5/0806 , C07K5/0812
摘要： Compounds represented by the general formula (1) or salts thereof or solvates of both; PAR-2 antagonists containing the compounds; and preventive or therapeutic agents for PAR-2 related diseases containing the antagonists as the active ingredient: (1) wherein R1 is hydrogen, halogeno, or a group represented by the general formula (2): (wherein R11 is straight-chain or branched C1-6 alkylene or the like; and R12 and R13 together with the nitrogen atom adjacent to them form a 5- to 7-membered ring); R2 is straight-chain or branched C1-6 alkyl or the like; R3 and R4 are each independently hydrogen, one to three halogen atoms, or the like; and A1-A2-A3 is a tripeptide residue composed of α-amino acids each independently selected from the group consisting of glycine, alanine, cyclohexylalanine, and so on.
摘要翻译：由通式（1）表示的化合物或其盐或两者的溶剂合物; 含有这些化合物的PAR-2拮抗剂; 以及含有拮抗剂作为活性成分的PAR-2相关疾病的预防或治疗剂：（1）其中R1是氢，卤素或由通式（2）表示的基团：（其中R11是直链或支链的 C 1-6亚烷基等; R 12和R 13与它们相邻的氮原子一起形成5-至7-元环）; R2是直链或支链C 1-6烷基等; R3和R4各自独立地为氢，一至三个卤素原子等; 并且A1-A2-A3是由各自独立地选自甘氨酸，丙氨酸，环己基丙氨酸等的α-氨基酸组成的三肽残基。

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