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1. 发明申请

US20090325992A1 COMPOUND HAVING CYCLIC GROUP BOUND THERETO THROUGH SPIRO BINDING AND USE THEREOF 审中-公开
标题翻译：具有通过螺旋结合的循环组合物的化合物及其用途
公开(公告)号：US20090325992A1
公开(公告)日：2009-12-31
申请号：US12375841
申请日：2007-07-30
申请人： Keisuke Hanada , Masaya Kokubo , Hiroshi Ochiai , Kousuke Tani , Shiro Shibayama
发明人： Keisuke Hanada , Masaya Kokubo , Hiroshi Ochiai , Kousuke Tani , Shiro Shibayama
IPC分类号： A61K31/438 , C07D471/10
CPC分类号： C07D471/04 , A61K45/06 , C07D401/12 , C07D471/10 , C07D487/10
摘要： A compound represented by general formula (I): a salt thereof, a solvate thereof, or a prodrug thereof wherein all symbols are as defined in the specification has an antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, retinopathy, macular degeneration, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiovascular disease, metabolic diseases, cancerous diseases (for example, cancer, cancer metastasis, etc.), a preventive and/or therapeutic agent for cancerous diseases or infections, or an agent for regeneration therapy.
摘要翻译：由通式（I）表示的化合物：其盐，其溶剂化物或前药，其中所有符号如本说明书中所定义，具有对CXCR4的拮抗活性，因此可用作预防和/或治疗剂 CXCR4介导的疾病，例如炎症和免疫疾病（例如类风湿性关节炎，关节炎，视网膜病变，黄斑变性，肺纤维化，移植器官排斥反应等），过敏性疾病，感染（例如，人类免疫缺陷病毒感染，获得性免疫缺陷综合征等），精神神经性疾病，脑疾病，心血管疾病，代谢疾病，癌性疾病（例如癌症，癌症转移等），癌性疾病或感染的预防和/或治疗剂，或再生治疗剂。

2. 发明授权

US08476290B2 Compound having spiro-bonded cyclic group and use thereof 失效
标题翻译：具有螺键的环状基团的化合物及其用途
公开(公告)号：US08476290B2
公开(公告)日：2013-07-02
申请号：US13378799
申请日：2010-06-15
申请人： Koji Yoshida , Hiroshi Ochiai , Kousuke Tani , Shiro Shibayama , Miki Kasano
发明人： Koji Yoshida , Hiroshi Ochiai , Kousuke Tani , Shiro Shibayama , Miki Kasano
IPC分类号： A61K31/438 , C07D471/10
CPC分类号： C07D471/10
摘要： A compound represented by formula (I): a salt thereof, an N-oxide thereof, or a solvate thereof (symbols in the formula are as described in the specification). The compounds of the present invention exhibit very low risk of side effects and also have persistent and strong antagonistic activity against CXCR4, and are therefore useful as pharmaceuticals, for example, as a preventive and/or therapeutic agent for inflammatory and immune diseases, infections (for example, HIV infection), diseases associated with HIV infection (for example, acquired immunodeficiency syndrome (AIDS)), cancer, cancer metastasis, psychoneurotic diseases and cardiovascular diseases (for example, retinopathy), metabolic diseases, cancerous diseases, or as an agent for regeneration therapy.
摘要翻译：由式（I）表示的化合物：其盐，其N-氧化物或其溶剂化物（式中的符号如说明书中所述）。本发明的化合物显示出非常低的副作用风险，并且对CXCR4具有持久和强烈的拮抗活性，因此可用作药物，例如作为炎症和免疫疾病，感染的预防和/或治疗剂（例如艾滋病毒感染），与艾滋病毒感染有关的疾病（例如，获得性免疫缺陷综合征（AIDS）），癌症，癌症转移，精神神经病和心血管疾病（例如视网膜病变），代谢疾病，癌性疾病或作为再生治疗剂。

3. 发明申请

US20120101280A1 COMPOUND HAVING SPIRO-BONDED CYCLIC GROUP AND USE THEREOF 失效
标题翻译：具有螺旋结合循环组的化合物及其用途
公开(公告)号：US20120101280A1
公开(公告)日：2012-04-26
申请号：US13378799
申请日：2010-06-15
申请人： Koji Yoshida , Hiroshi Ochiai , Kousuke Tani , Shiro Shibayama , Miki Kasano
发明人： Koji Yoshida , Hiroshi Ochiai , Kousuke Tani , Shiro Shibayama , Miki Kasano
IPC分类号： C07D471/10
CPC分类号： C07D471/10
摘要： The invention relates to a compound represented by formula (I): a salt thereof, an N-oxide thereof, or a solvate thereof (symbols in the formula are as described in the specification).The compound of the present invention exhibits very low risk of side effects and also has persistent and strong antagonistic activity against CXCR4, and is therefore useful as pharmaceuticals, for example, preventive and/or therapeutic agent for inflammatory and immune diseases, infections (for example, HIV infection), diseases associated with HIV infection (for example, acquired immunodeficiency syndrome (AIDS)), cancer, cancer metastasis, psychoneurotic diseases and cardiovascular diseases (for example, retinopathy), metabolic diseases, cancerous diseases, or an agent for regeneration therapy.
摘要翻译：本发明涉及由式（I）表示的化合物：其盐，其N-氧化物或其溶剂化物（式中的符号如说明书中所述）。本发明的化合物显示出非常低的副作用风险，并且对CXCR4具有持久和强烈的拮抗活性，因此可用作药物，例如用于炎症和免疫疾病，感染的预防和/或治疗剂（例如，艾滋病毒感染），与艾滋病毒感染有关的疾病（例如，获得性免疫缺陷综合征（AIDS）），癌症，癌症转移，精神神经病和心血管疾病（例如视网膜病变），代谢疾病，癌性疾病或再生药剂治疗。

4. 发明申请

US20140171388A1 COMPOUND FOR TREATING CARTILAGE DISORDERS 有权
标题翻译：化合物用于治疗消化系统疾病
公开(公告)号：US20140171388A1
公开(公告)日：2014-06-19
申请号：US14237037
申请日：2012-08-03
申请人： Tetsuo Obitsi , Kousuke Tani , Hikaru Sugihara , Akio Nishiura , Shinsei Fujimura
发明人： Tetsuo Obitsi , Kousuke Tani , Hikaru Sugihara , Akio Nishiura , Shinsei Fujimura
IPC分类号： C07C405/00 , C07C235/16 , C07C59/56 , C07C65/28
CPC分类号： C07C59/56 , A61K9/0019 , A61K47/26 , A61K47/6951 , C07C235/06 , C07C235/16 , C07C405/00 , C07C2601/04 , C07C2601/08 , Y10T428/2982
摘要： The present invention provides a compound of which active |form| is represented by a formula (A). and which can be injected into a joint cavity which is an affected part of disorders and can be accumulated in the joint cavity to exert the pharmacological effect thereof in a sustained manner, for the purpose of ameliorating cartilage disorders without developing any side effect. A compound according to the present invention, which is represented by a formula (I): (wherein all of symbols are as defined in the description), is a compound that can achieve the above-mentioned purpose. This compound does not exhibit any side effect on the cardiovascular system even when the compound is administered in an effective amount for exhibiting a cartilage regeneration activity, and is therefore extremely useful as a safe and effective preventive and/or therapeutic agent for cartilage disorders. Since a suspension produced using this compound can be injected without requiring the incision of the affected part, it can reduce the burden on patients, and is extremely useful as a medicinal agent.
摘要翻译：本发明提供了一种活性成分的化合物由式（A）表示。并且其可以注射到作为疾病的一部分的关节腔中，并且可以以持续的方式累积在关节腔中以发挥其药理作用，以改善软骨疾病而不产生副作用。由式（I）表示的本发明化合物（其中所有符号如说明书中所定义）是可以实现上述目的的化合物。即使当化合物以有效量施用以显示软骨再生活性时，该化合物也不会对心血管系统显示任何副作用，因此作为软骨疾病的安全有效的预防和/或治疗剂非常有用。由于使用该化合物制备的悬浮液可以不需要切开患者部位而被注射，所以能够减轻患者的负担，作为药剂非常有用。

5. 发明授权

US08026273B2 8-azaprostaglandin derivative compound and agent comprising the compound as active ingredient 失效
标题翻译： 8-氮杂的前列腺素衍生物化合物和包含该化合物作为活性成分的试剂
公开(公告)号：US08026273B2
公开(公告)日：2011-09-27
申请号：US12683609
申请日：2010-01-07
申请人： Kousuke Tani , Kaoru Kobayashi , Toru Maruyama , Tohru Kambe , Mikio Ogawa , Tsutomu Shiroya
发明人： Kousuke Tani , Kaoru Kobayashi , Toru Maruyama , Tohru Kambe , Mikio Ogawa , Tsutomu Shiroya
IPC分类号： A61K31/40 , A61K31/405 , C07D207/00 , C07D209/00
CPC分类号： C07D413/06 , C07D207/26 , C07D263/24 , C07D405/06 , C07D405/12 , C07D409/06 , C07D409/12 , C07D413/12 , C07D417/06 , C07D417/12
摘要： An 8-azaprostaglandin represented by formula (I) (wherein all symbols have the same meanings as described in the specification), a pharmaceutically acceptable salt thereof or a cyclodextrin clathrate thereof. Since the compound represented by formula (I) binds to EP2 subtype among PGE receptor strongly, it is useful for preventive and/or treatment for immune diseases, allergic diseases, neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy such as glaucoma, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis, renal failure, circulatory diseases, systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, or bone diseases etc.
摘要翻译：由式（I）（其中所有符号具有与说明书中所述相同的含义）表示的8-氮杂前列腺素，其药学上可接受的盐或其环糊精包合物。由于式（I）表示的化合物强烈地与PGE受体中的EP2亚型结合，因此可用于免疫疾病，过敏性疾病，神经元细胞死亡，痛经，早产，流产，秃发，视网膜神经病变等的预防和/或治疗青光眼，勃起功能障碍，关节炎，肺损伤，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺病，肝损伤，急性肝炎，肝硬化，休克，肾炎，肾衰竭，循环系统疾病，全身性炎症反应综合征，败血症，血细胞增多综合征，巨噬细胞活化综合征，静止病，川崎病，烧伤，全身肉芽肿，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭或骨骼疾病等。

6. 发明申请

US20050124577A1 8-Azaprostaglandin derivative compounds and drugs containing the compounds as the active ingredient 失效
标题翻译： 8-Azaprostaglandin衍生物化合物和含有这些化合物作为活性成分的药物
公开(公告)号：US20050124577A1
公开(公告)日：2005-06-09
申请号：US10506536
申请日：2003-03-04
申请人： Kousuke Tani , Kaoru Kobayashi , Toru Maruyama , Tohru Kambe , Mikio Ogawa , Tsutomu Shiroya
发明人： Kousuke Tani , Kaoru Kobayashi , Toru Maruyama , Tohru Kambe , Mikio Ogawa , Tsutomu Shiroya
IPC分类号： C07D207/27 , A61P1/00 , A61P1/16 , A61P7/00 , A61P9/00 , A61P9/08 , A61P9/10 , A61P9/12 , A61P11/00 , A61P11/06 , A61P11/08 , A61P13/12 , A61P15/06 , A61P15/10 , A61P19/02 , A61P19/08 , A61P19/10 , A61P25/00 , A61P27/02 , A61P29/00 , A61P35/00 , A61P37/02 , A61P43/00 , C07D207/26 , C07D263/24 , C07D405/06 , C07D405/12 , C07D409/06 , C07D409/12 , C07D413/06 , C07D413/12 , C07D417/06 , C07D417/12 , A61K31/724 , A61K31/557 , C07D413/02 , C07D417/02
CPC分类号： C07D413/06 , C07D207/26 , C07D263/24 , C07D405/06 , C07D405/12 , C07D409/06 , C07D409/12 , C07D413/12 , C07D417/06 , C07D417/12
摘要： An 8-azaprostaglandin represented by formula (I) (wherein all symbols have the same meanings as described in the specification), a pharmaceutically acceptable salt thereof or a cyclodextrin clathrate thereof. Since the compound represented by formula (I) binds to EP2 subtype among PGE receptor strongly, it is useful for preventive and/or treatment for immune diseases, allergic diseases, neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy such as glaucoma, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis, renal failure, circulatory diseases, systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, or bone diseases etc.
摘要翻译：由式（I）（其中所有符号具有与说明书中所述相同的含义）表示的8-氮杂前列腺素，其药学上可接受的盐或其环糊精包合物。由于式（I）表示的化合物强烈地与PGE受体中的EP2亚型结合，因此可用于免疫疾病，过敏性疾病，神经元细胞死亡，痛经，早产，流产，秃发，视网膜神经病变等的预防和/或治疗青光眼，勃起功能障碍，关节炎，肺损伤，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺病，肝损伤，急性肝炎，肝硬化，休克，肾炎，肾衰竭，循环系统疾病，全身性炎症反应综合征，败血症，血细胞增多综合征，巨噬细胞活化综合征，静止病，川崎病，烧伤，全身肉芽肿，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭或骨骼疾病等。

7. 发明授权

US07491748B2 Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient 失效
标题翻译：羧酸衍生物化合物和包含这些化合物作为活性成分的药物
公开(公告)号：US07491748B2
公开(公告)日：2009-02-17
申请号：US10486220
申请日：2002-08-08
申请人： Kousuke Tani , Masaki Asada , Kaoru Kobayashi , Masami Narita , Mikio Ogawa
发明人： Kousuke Tani , Masaki Asada , Kaoru Kobayashi , Masami Narita , Mikio Ogawa
IPC分类号： A61K31/195 , C07C229/02
CPC分类号： C07D231/12 , C07C59/68 , C07C69/734 , C07C69/736 , C07C69/738 , C07C229/34 , C07C309/66 , C07C309/67 , C07C309/73 , C07C311/06 , C07C311/08 , C07C311/19 , C07C311/29 , C07C311/51 , C07C317/18 , C07C317/22 , C07C317/40 , C07C317/50 , C07C323/19 , C07C323/42 , C07C323/59 , C07C323/60 , C07D233/56 , C07D249/08
摘要： A carboxylic acid derivative of formula (I): wherein R1 is —COOH, —COOR6, etc.; A is a single bond, alkylene, etc.; R2 is alkyl, alkoxy, etc.; B is a carbocyclic ring or a heterocyclic ring; Q is alkylnene-Cyc2, etc.; D is a linking chain; and R3 is alkyl, a carbocyclic ring or a heterocyclic ring, or a non-toxic salt thereof. The compound of formula (I) binds to PGE2 receptor, especially subtypes EP3 and/or EP4 and show the antagonizing activity, are useful for the prevention and/or treatment of diseases induced pain, itch, urticaria, allergy, urinary frequency, urinary disturbance, Alzheimer's disease, cancer, dysmenorrhea, endometriosis, etc.
摘要翻译：式（I）的羧酸衍生物：其中R 1是-COOH，-COOR 6等; A是单键，亚烷基等; R2是烷基，烷氧基等; B是碳环或杂环; Q是亚烷基-Si 2等; D是连接链; 和R 3是烷基，碳环或杂环，或其无毒盐。式（I）化合物与PGE2受体结合，特别是亚型EP3和/或EP4并显示拮抗活性，可用于预防和/或治疗疾病诱发的疼痛，瘙痒，荨麻疹，过敏，尿频，尿紊乱，阿尔茨海默病，癌症，痛经，子宫内膜异位症等

8. 发明授权

US06576785B1 &ohgr;-cycloalkyl-prostaglandin E2 derivatives 失效
标题翻译： ω-环烷基 - 前列腺素E2衍生物
公开(公告)号：US06576785B1
公开(公告)日：2003-06-10
申请号：US09570728
申请日：2000-05-12
申请人： Kousuke Tani , Shuichi Ohuchida
发明人： Kousuke Tani , Shuichi Ohuchida
IPC分类号： C07C40500
CPC分类号： C07C405/00
摘要： A &ohgr;-cycloalkyl-prostaglandin E2 derivatives of the formula (I) wherein R is carboxy or hydroxymethyl; R1 is oxo, methylene or halogen atom; R2 is H, OH or C1-4 alkoxy; R3 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkoxy, C3-7 cycloalkyl, phenyl, or phenyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkyl, C1-4 alkoxy, nitro, trifluoromethyl; n is 0-4; and non-toxic salt thereof, prodrug thereof and cyclodextrin clathrate thereof can strongly bind on EP2 subtype receptor. Therefore, they are useful for prevention and/or treatment of immune disease (autoimmune disease, organ transplantation, etc.), asthma, abnormal bone formation, neuron cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc.
摘要翻译：式（I）的ω-环烷基 - 前列腺素E2衍生物，其中R是羧基或羟甲基; R1是氧代，亚甲基或卤素原子; R2是H，OH或C1-4烷氧基; R 3为H，C 1-8烷基，C 2-8烯基，C 2-8炔基，C 1-8烷基，C 2-8烯基或被1-3个选自卤素原子，C 1-4烷氧基， C 3-7环烷基，苯基或被1-3个选自卤素原子，C 1-4烷基，C 1-4烷氧基，硝基，三氟甲基的取代基取代的苯基; n为0-4;其无毒盐，其前药和环糊精包合物可以强烈结合EP2亚型受体。因此，它们可用于预防和/或治疗青光眼等免疫疾病（自身免疫性疾病，器官移植等），哮喘，异常骨形成，神经细胞死亡，肝损伤，流产，早产或视网膜神经病变等。

9. 发明申请

US20120122964A1 BICYCLIC COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES 有权
标题翻译：双相化合物及其用途用于医疗用途
公开(公告)号：US20120122964A1
公开(公告)日：2012-05-17
申请号：US13384383
申请日：2010-07-27
申请人： Tohru Kambe , Toru Maruyama , Shinsaku Yamane , Satoshi Nakayama , Kousuke Tani
发明人： Tohru Kambe , Toru Maruyama , Shinsaku Yamane , Satoshi Nakayama , Kousuke Tani
IPC分类号： A61K31/335 , A61P27/12 , A61P27/06 , C07D313/06 , A61P27/02
CPC分类号： A61K31/335 , A61K9/0048 , A61K31/4427 , A61K31/558 , C07D313/06 , C07D401/06 , C07D405/06 , C07D407/12 , C07D417/04
摘要： Since a compound represented by the general formula (I) (wherein definition of each group is as described in the specification), a salt thereof, a solvate thereof, or a prodrug thereof has strong and sustaining intraocular pressure lowering activity and, further, has no side effect on eyes such as ocular stimulating property (hyperemia, corneal clouding etc.), aqueous humor protein rise etc., it has high safety, and can be an excellent agent for preventing and/or treating glaucoma etc.
摘要翻译：由于由通式（I）表示的化合物（其中每个基团的定义如说明书中所述），其盐，其溶剂化物或其前药具有强的和持续的眼内压降低活性，并且还具有对眼睛没有副作用，如眼刺激性（充血，角膜混浊等），房水蛋白上升等，具有高度的安全性，可以作为预防和/或治疗青光眼等的优异剂。

10. 发明授权

US07858650B2 Medicinal composition for inhalation 失效
标题翻译：吸入药物成分
公开(公告)号：US07858650B2
公开(公告)日：2010-12-28
申请号：US11665966
申请日：2005-10-21
申请人： Shigeki Yamamoto , Tsutomu Shiroya , Michiaki Kadode , Toru Maruyama , Kousuke Tani , Toshihiko Nagase
发明人： Shigeki Yamamoto , Tsutomu Shiroya , Michiaki Kadode , Toru Maruyama , Kousuke Tani , Toshihiko Nagase
IPC分类号： A61K31/427 , C07D277/36
CPC分类号： A61K31/427 , A61K31/00 , A61K45/06 , C07D417/12
摘要： A medicinal composition for inhalation containing a continuous-release type prodrug of an EP2 agonist topically exhibits a prolonged bronchodilating and antiinflammatory effects. Namely, the medicinal composition for inhalation containing a continuous-release type prodrug of an EP2 agonist is useful as a safe preventive and/or a remedy for respiratory diseases (for example, asthma, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, adult respiratory distress syndrome, cystic fibrosis, pulmonary hypertension or the like) without causing any systemic effect such as lowering blood pressure. Thus, a safe and useful remedy for respiratory diseases is provided.
摘要翻译：含有EP2激动剂的连续释放型前药的用于吸入的药物组合物局部显示出延长的支气管扩张和抗炎作用。即，含有EP2激动剂的连续释放型前药的吸入药物组合物可用作呼吸系统疾病的安全预防和/或补救措施（例如，哮喘，肺损伤，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺疾病，成人呼吸窘迫综合征，囊性纤维化，肺动脉高压等），而不引起诸如降低血压的全身作用。因此，提供了一种安全有效的呼吸系统疾病补救措施。

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