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1. 发明申请

WO03049723A8 USE OF PROTEASE-ACTIVATED RECEPTOR-2 INHIBITOR IN THE MANIFACTURE OF A MEDICAMENT FOR TREATING DELAYED HYPERSENSITIVITY 审中-公开
标题翻译：用于治疗迟发性高血压的药物制剂中使用激素受体2抑制剂
公开(公告)号：WO03049723A8
公开(公告)日：2004-04-15
申请号：PCT/GB0205658
申请日：2002-12-13
申请人： KOWA CO , TAKIZAWA TOSHIAKI , TAMIYA MASAKI , SAITO NAOHIRO , KANKE TORU , MATSUMOTO JIRO , WADA YASUSHI , KAWAGOE JUNICHI , FERRELL WILLIAM R , LOCKHART JOHN C
发明人： TAKIZAWA TOSHIAKI , TAMIYA MASAKI , SAITO NAOHIRO , KANKE TORU , MATSUMOTO JIRO , WADA YASUSHI , KAWAGOE JUNICHI , FERRELL WILLIAM R , LOCKHART JOHN C
IPC分类号： G01N33/50 , A61K31/00 , A61K45/00 , A61K45/06 , A61P1/04 , A61P3/10 , A61P11/06 , A61P17/00 , A61P19/02 , A61P19/06 , A61P21/04 , A61P29/00 , A61P31/06 , A61P33/12 , A61P35/00 , A61P37/02 , A61P37/06 , A61P37/08 , C12N15/09 , C12Q1/02 , G01N33/15 , A61K38/00 , C12Q1/37 , G01N33/68
CPC分类号： A61K45/06 , A61K31/00 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition by a novel action mechanism without serious side effects for delayed hypersensitivity and a screening method of the same. The invention also provides a novel assay method of inhibitors/suppressive agents of PAR-2. The invention relates to a pharmaceutical composition for delayed hypersensitivity containing one or two or more active ingredients selected from the group consisting of inhibitors of PAR-2 and suppressive agents of PAR-2 gene expression and a pharmaceutically acceptable carrier, and to a method for screening active ingredients for pharmaceutical composition for delayed hypersensitivity by contacting a subject substance with cells expressing PAR-2 and by determining expression or activity of PAR-2. The invention also relates to a method for detecting or quantifying actions of the subject substance for PAR-2 using cells expressing PAR-2 in a culture containing inositol.
摘要翻译：本发明通过新颖的作用机理提供药物组合物，对迟发性超敏反应没有严重的副作用及其筛选方法。本发明还提供了PAR-2抑制剂/抑制剂的新型测定方法。本发明涉及一种用于延迟超敏反应的药物组合物，其含有选自PAR-2的抑制剂和PAR-2基因表达的抑制剂的一种或两种以上活性成分和药学上可接受的载体，以及筛选方法通过使受试物质与表达PAR-2的细胞接触并通过测定PAR-2的表达或活性来延迟超敏反应的药物组合物的活性成分。本发明还涉及使用含有肌醇的培养物中表达PAR-2的细胞检测或定量PAR-2的物质的作用的方法。

2. 发明申请

WO03049723A2 PHARMACEUTICAL COMPOSITION FOR DELAYED HYPERSENSITIVITY 审中-公开
标题翻译：用于延迟超敏性的药物组合物
公开(公告)号：WO03049723A2
公开(公告)日：2003-06-19
申请号：PCT/GB0205658
申请日：2002-12-13
申请人： KOWA CO , TAKIZAWA TOSHIAKI , TAMIYA MASAKI , SAITO NAOHIRO , KANKE TORU , MATSUMOTO JIRO , WADA YASUSHI , KAWAGOE JUNICHI , FERRELL WILLIAM R , LOCKHART JOHN C
发明人： TAKIZAWA TOSHIAKI , TAMIYA MASAKI , SAITO NAOHIRO , KANKE TORU , MATSUMOTO JIRO , WADA YASUSHI , KAWAGOE JUNICHI , FERRELL WILLIAM R , LOCKHART JOHN C
IPC分类号： G01N33/50 , A61K31/00 , A61K45/00 , A61K45/06 , A61P1/04 , A61P3/10 , A61P11/06 , A61P17/00 , A61P19/02 , A61P19/06 , A61P21/04 , A61P29/00 , A61P31/06 , A61P33/12 , A61P35/00 , A61P37/02 , A61P37/06 , A61P37/08 , C12N15/09 , C12Q1/02 , G01N33/15 , A61K38/00 , C12Q1/37
CPC分类号： A61K45/06 , A61K31/00 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition by a novel action mechanism without serious side effects for delayed hypersensitivity and a screening method of the same. The invention also provides a novel assay method of inhibitors/suppressive agents of PAR-2. The invention relates to a pharmaceutical composition for delayed hypersensitivity containing one or two or more active ingredients selected from the group consisting of inhibitors of PAR-2 and suppressive agents of PAR-2 gene expression and a pharmaceutically acceptable carrier, and to a method for screening active ingredients for pharmaceutical composition for delayed hypersensitivity by contacting a subject substance with cells expressing PAR-2 and by determining expression or activity of PAR-2. The invention also relates to a method for detecting or quantifying actions of the subject substance for PAR-2 using cells expressing PAR-2 in a culture containing inositol.
摘要翻译：本发明通过新颖的作用机理提供药物组合物，对迟发性超敏反应没有严重的副作用及其筛选方法。本发明还提供了PAR-2抑制剂/抑制剂的新型测定方法。本发明涉及一种用于延迟超敏反应的药物组合物，其含有选自PAR-2的抑制剂和PAR-2基因表达的抑制剂的一种或两种以上活性成分和药学上可接受的载体，以及筛选方法通过使受试物质与表达PAR-2的细胞接触并通过测定PAR-2的表达或活性来延迟超敏反应的药物组合物的活性成分。本发明还涉及使用含有肌醇的培养物中表达PAR-2的细胞检测或定量PAR-2的物质的作用的方法。

3. 发明申请

WO1996020177A1 PYRIMIDINE DERIVATIVES 审中-公开
标题翻译：吡嗪衍生物
公开(公告)号：WO1996020177A1
公开(公告)日：1996-07-04
申请号：PCT/JP1995002605
申请日：1995-12-19
申请人： KOWA CO., LTD. , HIRATA, Mitsuteru , DEUSHI, Takeo , TAKAHASHI, Yoshio , TAMURA, Masahiro , OHSHIMA, Takeshi , ODA, Toshiaki , SONOKI, Hiroyuki , SHIRATSUCHI, Masami
发明人： KOWA CO., LTD.
IPC分类号： C07D239/52
CPC分类号： C07D239/69
摘要： A pyrimidine derivative represented by general formula (1) or a salt thereof and a medicine comprising the same as the active ingredient, wherein R represents lower alkyl; R and R represent each hydrogen, alkyl or alkoxy; R and R represent each hydrogen or alkyl; R represents alkyl, -OR or NR N ; and n represents a number of 0 to 3 (wherein R , R and R represent each hydrogen, alkyl, aryl, aralkyl, amino, heterocycle, etc.). The compound has a potent inhibitory activity on endothelin having potent vasoconstrictor and cell proliferation effects and is useful in treating circulatory disorders, etc.
摘要翻译：由通式（1）表示的嘧啶衍生物或其盐和含有该活性成分的药物，其中R 1表示低级烷基; R 2和R 3各自代表氢，烷基或烷氧基; R 4和R 5各自代表氢或烷基; R 6表示烷基，-OR 7或NR 8 N 9; n表示0〜3的数（式中，R 7，R 8，R 9表示氢，烷基，芳基，芳烷基，氨基，杂环等）。该化合物对具有有效的血管收缩剂和细胞增殖作用的内皮素具有有效的抑制活性，可用于治疗循环障碍等。

4. 发明申请

WO1994026768A1 OSTEOGENESIS PROMOTER AND OSTEOPOROSIS REMEDY 审中-公开
标题翻译： OSTEOGENESIS PROMOTER和OSTEOPOROSIS救济
公开(公告)号：WO1994026768A1
公开(公告)日：1994-11-24
申请号：PCT/JP1994000798
申请日：1994-05-18
申请人： LTT INSTITUTE CO., LTD. , KOWA CO., LTD. , TEIJIN LIMITED , SUZUKI, Yasuo , MIZUSHIMA, Yutaka
发明人： LTT INSTITUTE CO., LTD. , KOWA CO., LTD. , TEIJIN LIMITED
IPC分类号： C07J01/00
CPC分类号： A61K31/5685 , A61K31/565
摘要： An osteogenesis promoter and/or an osteoporosis remedy containing an androgen derivative represented by general formula (1) or a salt thereof as the active ingredient. In said formula (1), the broken lines indicate that the bonds containing the same represent each either a single or a double bond. The compound (1) activates osteoblasts, promotes osteogenesis and increases bone quantity, and hence it is used for treating a morbid condition of lowered osteogenesis due to aging, immobilization, administration of glucocorticoids, and so forth. Further it can increase bone quantity by the osteogenesis promoter effect thereof, so that it is useful for treating osteoporosis accompanying the above morbid condition or occurring after ovariectomy or menopause.
摘要翻译：含有通式（1）表示的雄激素衍生物或其盐作为活性成分的成骨促进剂和/或骨质疏松症药物。在所述式（1）中，虚线表示含有该键的键各自表示单键或双键。化合物（1）激活成骨细胞，促进成骨并增加骨量，因此用于治疗由老化，固定化，糖皮质激素等引起的降低成骨的病态。此外，它可以通过骨形成促进剂效应增加骨量，从而可用于治疗伴随上述病态的骨质疏松症或卵巢切除术或绝经后发生的骨质疏松症。

5. 发明申请

WO2011105099A8 COMPOUND CONTAINING A NOVEL 4-ALKOXYPYRIMIDINE FORMATION AND MEDICINE CONTAINING SAME 审中-公开
标题翻译：含有新型4-烷氧基嘧啶形成的化合物和含有其的药物
公开(公告)号：WO2011105099A8
公开(公告)日：2012-08-16
申请号：PCT/JP2011001086
申请日：2011-02-25
申请人： KOWA CO , MIURA TORU , ONOGI KAZUHIRO , TAGASHIRA JUNYA , WATANABE GEN , SEKIMOTO RYOHEI , ISHIDA RIE , AOKI HITOMI , OHGIYA TADAAKI
发明人： MIURA TORU , ONOGI KAZUHIRO , TAGASHIRA JUNYA , WATANABE GEN , SEKIMOTO RYOHEI , ISHIDA RIE , AOKI HITOMI , OHGIYA TADAAKI
IPC分类号： C07D413/10 , A61K31/506 , A61K31/5377 , A61P3/04 , A61P3/10 , A61P9/00 , A61P9/10 , A61P9/12 , A61P13/12 , A61P25/00 , A61P27/02 , A61P43/00 , C07D413/14
CPC分类号： C07D413/10 , C07D413/14
摘要： Disclosed is novel compound and medicinal formulation containing same, possessing both angiotensin II receptor blocking and PPAR? activation effect, of use as a medicine for prevention and/or treatment of hypertension, heart disease, angina pectoris, cerebrovascular disorder, cerebral circulatory disturbances, post-ischemic peripheral circulatory damage, renal disease, arteriosclerosis, inflammatory disorder, type 2 diabetes, diabetic complications, insulin resistance syndrome, syndrome X, metabolic syndrome and hyperinsulinaemia. Further disclosed is the general formula I (where one or both of R1 and R2 represent a C1-6 alkyl group, R3 represents a C1-6 alkyl group which may contain one or more substituent groups selected from group A, or a C3-8 cycloalkyl group which may contain one or more substituent groups selected from group B.) which represents the compound, and salts thereof, solvates thereof, and medicinal compositions containing any of these.
摘要翻译：公开了含有它们的新型化合物和药物制剂，具有血管紧张素II受体阻断和PPAR？激活效应，用作预防和/或治疗高血压，心脏病，心绞痛，脑血管障碍，脑循环障碍，缺血后外周循环损伤，肾脏疾病，动脉硬化，炎症性疾病，2型糖尿病，糖尿病并发症，胰岛素抵抗综合征，X综合症，代谢综合征和高胰岛素血症。进一步公开的是通式I（其中R 1和R 2中的一个或两个表示C 1-6烷基，R 3表示可以含有一个或多个选自A组的取代基的C 1-6烷基或C 3-8 可以含有一个或多个选自B组的取代基的环烷基），其代表该化合物及其盐，其溶剂合物，以及含有这些中的任何一种的药物组合物。

6. 发明申请

WO2006064889A1 METHOD FOR REDUCTION, STABILIZATION AND PREVENTION OF RUPTURE OF LIPID RICH PLAQUE 审中-公开
标题翻译：减少，稳定和防止破碎的富含PLAQUE的方法
公开(公告)号：WO2006064889A1
公开(公告)日：2006-06-22
申请号：PCT/JP2005/023088
申请日：2005-12-09
申请人： KOWA CO., LTD. , KOBAYASHI, Hideyuki , YOSHINAKA, Yasunobu , SHIBUYA, Kimiyuki
发明人： KOBAYASHI, Hideyuki , YOSHINAKA, Yasunobu , SHIBUYA, Kimiyuki
IPC分类号： A61K31/497 , A61K31/47 , A61P9/10
CPC分类号： A61K31/497 , A61K31/47 , A61K2300/00
摘要： There is to provide is an agent for reduction of a lipid rich plaque, stabilization of a lipid rich plaque and/or prevention of rupture of a lipid rich plaque in an atherosclerotic lesion comprising an effective amount of 2-[4-[2-(benzimidazole-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide (hereinafter, referred to as compound 1), its pharmaceutically acceptable salt or a hydrate thereof and Pitavastatin, and a pharmaceutically acceptable carrier, wherein the agent is intended to be simultaneously administered, or separately administered with interval of time to a patient in need thereof. There is also to provide a method for reduction of a lipid rich plaque, stabilization of a lipid rich plaque and/or prevention of rupture of a lipid rich plaque in an atherosclerotic lesion, comprising simultaneously administering, or separately administering with interval of time an effective amount of the compound 1, its pharmaceutically acceptable salt or a hydrate thereof and an effective amount of Pitavastatin to a patient in need thereof.
摘要翻译：提供的是减少富含脂质的斑块，稳定富含脂质的斑块和/或预防动脉粥样硬化病变中脂质丰富斑块破裂的药剂，其包含有效量的2- [4- [2-（苯并咪唑-2-基硫基）乙基]哌嗪-1-基] -N- [2,4-双（甲硫基）-6-甲基-3-吡啶基]乙酰胺（以下称为化合物1），其药学上可接受的盐或其水合物和匹伐他汀，以及药学上可接受的载体，其中所述试剂旨在同时施用，或者分开施用于有需要的患者的时间间隔。还提供减少富含脂质的斑块，稳定富含脂质的斑块和/或防止动脉粥样硬化病变中富含脂质斑块的破裂的方法，其包括同时施用或分开施用一段时间间隔的有效化合物1的量，其药学上可接受的盐或其水合物和有效量的匹伐他汀给有需要的患者。

7. 发明申请

WO2005063294A8 INHIBITOR FOR THE FORMATION OF gamma-SECRETASE COMPLEX 审中-公开
标题翻译：抑制剂，用于形成γ-分泌酶复合物
公开(公告)号：WO2005063294A8
公开(公告)日：2005-10-06
申请号：PCT/JP2004019628
申请日：2004-12-28
申请人： KOWA CO , NISSAN CHEMICAL IND LTD , URANO YASUOMI , HAMAKUBO TAKAO , KODAMA TATSUHIKO
发明人： URANO YASUOMI , HAMAKUBO TAKAO , KODAMA TATSUHIKO
IPC分类号： A61K31/135 , A61K31/35 , A61K31/47 , A61K31/724 , A61K45/00 , A61K45/06 , A61P25/28 , A61P43/00 , C12Q1/00
CPC分类号： A61K31/135 , A61K31/35 , A61K31/47 , A61K31/724 , A61K45/06 , A61K2300/00
摘要： It is intended to provide an inhibitor for the formation of a gamma-secretase complex which comprises a cholesterol synthesis inhibitor or a protein geranylgeranylation regulator as the active ingredient; and use of a cholesterol synthesis inhibitor or a protein geranylgeranylation regulator for producing the same. It is also intended to provide a method of screening a substance having an effect of inhibiting the formation of an active complex of gamma-secretase which comprises assaying the activity of inhibiting cholesterol synthesis or quantifying cholesterol accumulated in lipid rafts in cells. It is also intended to provide a method of screening a cholesterol synthesis inhibitor, a protein geranylgeranylation regulator or an HMG-CoA reductase inhibitor which comprises assaying the effect of inhibiting the formation of an active complex of gamma-secretase. Moreover, it is intended to provide a method of screening an effect of a test substance on gamma-secretase which comprises measuring the distribution of constituents (niscastrin, APH-1, Pen-2 and so on) required by gamma-secretase for the formation of its active complex in cells.
摘要翻译：旨在提供形成γ-分泌酶复合物的抑制剂，其包含胆固醇合成抑制剂或蛋白质香叶基香叶基化调节剂作为活性成分; 以及使用胆固醇合成抑制剂或蛋白质香叶基香叶基化调节剂来生产它们。还打算提供筛选具有抑制γ-分泌酶活性复合物形成作用的物质的方法，其包括测定抑制胆固醇合成的活性或定量细胞中脂质筏中积累的胆固醇。还旨在提供一种筛选胆固醇合成抑制剂，蛋白质香叶基香叶基ge牛儿基化调节剂或HMG-CoA还原酶抑制剂的方法，其包括测定抑制γ-分泌酶活性复合物形成的作用。此外，意图提供一种筛选测试物质对γ-分泌酶的作用的方法，其包括测量γ-分泌酶对于形成所需的成分（niscastrin，APH-1，Pen-2等）的分布它在细胞中的活性复合物。

8. 发明申请

WO1998007702A1 DIAMIDE COMPOUNDS AND DRUGS CONTAINING THE SAME 审中-公开
标题翻译： DIAMIDE化合物和含有其的药物
公开(公告)号：WO1998007702A1
公开(公告)日：1998-02-26
申请号：PCT/JP1997002882
申请日：1997-08-20
申请人： KOWA CO., LTD. , ISHIWATA, Hiroyuki , KABEYA, Mototsugu , SHIGYO, Hiromichi , SHIRATSUCHI, Masami , HATTORI, Yukio , NAKAO, Hiroshi , NAGOYA, Takao , SATO, Seiichi , ODA, Soichi , SUDA, Makoto , SHIBASAKI, Manabu
发明人： KOWA CO., LTD.
IPC分类号： C07D215/12
CPC分类号： C07D213/69 , C07D213/56 , C07D213/70 , C07D213/82 , C07D215/12 , C07D231/12 , C07D233/56 , C07D241/04 , C07D241/42 , C07D243/08 , C07D249/08 , C07D295/185 , C07D471/04 , C07D487/04
摘要： Diamide derivatives represented by general formula (1), wherein A represents optionally substituted phenyl, etc.; B represents -CH=CH-, -CC-, -(CH=CH)2-, -CC-CH=CH-, -CH=CH-CC-, phenylene, etc.; and W represents (a) or (b). Because of having excellent inhibitory effects on the production of an IgE antibody, these compounds are useful as antiallergic agents, etc.
摘要翻译：由通式（1）表示的二酰胺衍生物，其中A表示任选取代的苯基等; B表示-CH = CH-，-CC-， - （CH = CH）2 - ，-CC-CH = CH-，-CH = CH-CC-，亚苯基等; W表示（a）或（b）。由于对IgE抗体的产生具有优异的抑制作用，所以这些化合物可用作抗过敏剂等。

9. 发明申请

WO1992008475A1 THERAPEUTIC AGENT FOR SKIN OR CORNEAL DISEASE 审中-公开
标题翻译：皮肤或角膜疾病治疗药物
公开(公告)号：WO1992008475A1
公开(公告)日：1992-05-29
申请号：PCT/JP1991001587
申请日：1991-11-19
申请人： KOWA CO., LTD. , JURIDICAL FOUNDATION THE CHEMO-SERO-THERAPEUTIC ... , NAKAO, Hiroshi , NAGOYA, Takao , SAINO, Yushi
发明人： KOWA CO., LTD. , JURIDICAL FOUNDATION THE CHEMO-SERO-THERAPEUTIC ...
IPC分类号： A61K37/02
CPC分类号： A61K38/1709
摘要： A therapeutic agent for skin or corneal diseases containing as the active ingredient CPB-1 or recombinant CPB-1, both of which are excellent in the activities of promoting neoformation of granulations of fibroblast, extending corneal endothelial and epithelial cells, etc., and lowering PKC activity. Because this agent has an action mechanism different from that of the conventional agent, it can be used together with the conventional agent to enhance the therapeutic effect, thus being remarkably useful for treating all sorts of the skin and corneal diseases, in particular, wound and psoriasis.

10. 发明申请

WO2003104213A1 PREPARATION PROCESS OF BIPHENYLCARBOXYLIC ACID AMIDE DERIVATIVES 审中-公开
标题翻译：联苯酰羧酸酰胺衍生物的制备方法
公开(公告)号：WO2003104213A1
公开(公告)日：2003-12-18
申请号：PCT/JP2003/007125
申请日：2003-06-05
申请人： KOWA CO., LTD.
发明人： ISHIWATA, Hiroyuki , SATO, Seiichi , KABEYA, Mototsugu , ODA, Soichi
IPC分类号： C07D295/18
CPC分类号： C07D295/192
摘要： A process for preparing a biphenylcarboxylic acid amide derivative represented by the following formula (1): wherein, R 1 , R 2 and R 3 each independently represents a hydrogen atom or a substituent, which comprises reacting, in the presence of a metal catalyst, a halogenobenzoic acid derivative represented by the following formula (2):wherein, X represents a halogen atom with a compound represented by the following formula (3): wherein, R 1 , R 2 and R 3 have the same meanings as described above, and Y represents an leaving group having an element selected from the group consisting of boron, silicon, zinc, tin and magnesium; or salt thereof.According to the present invention, biphenylcarboxylic acid amide derivatives of the formula (1) or salts thereof having excellent inhibitory activity against IgE antibody production can be prepared by the reduced number of steps, conveniently, at lower cost and in a high yield.2
摘要翻译：一种制备由下式（1）表示的联苯羧酸酰胺衍生物的方法：其中，R 1，R 2和R 3各自独立地表示氢原子或取代基，其包括在金属催化剂存在下，将卤代苯甲酸由下式（2）表示的衍生物：其中，X表示与下述式（3）表示的化合物相同的卤素原子：式中，R1，R2和R3与上述相同，Y表示离去基团具有选自硼，硅，锌，锡和镁的元素; 或其盐。根据本发明，具有优异的抗IgE抗体产生抑制活性的式（1）的联苯基羧酸酰胺衍生物或其盐可以通过减少数量的步骤，以较低的成本和较高的成本 yield.2

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