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1. 发明授权

US08329420B2 Screening method for a substance that binds to an intracellular region of TLR4 失效
标题翻译：结合TLR4细胞内区域的物质的筛选方法
公开(公告)号：US08329420B2
公开(公告)日：2012-12-11
申请号：US12225721
申请日：2007-03-29
申请人： Osamu Hazeki , Kaoru Hazeki , Masayuki Ii , Naoko Matsunaga
发明人： Osamu Hazeki , Kaoru Hazeki , Masayuki Ii , Naoko Matsunaga
IPC分类号： G01N33/567 , C12N1/21 , C12N1/19 , C12N5/10 , C12N5/16 , C12N5/18 , C12N5/22 , C07K14/705
CPC分类号： G01N33/566 , G01N2333/70596 , G01N2500/04 , G01N2500/10
摘要： The present invention provides a method of screening for a drug for the prophylaxis or treatment of at least one disease selected from the group consisting of cardiac disease, autoimmune disease, inflammatory disease, central nervous system disease, infectious disease, sepsis, severe sepsis and septic shock, which includes selecting a substance that binds to an intracellular region of TLR4, and inhibits signal transduction from said molecule, and a kit for this method, which contains (1) a cell that expresses wild-type TLR4 and (2) a cell that expresses a mutant TLR4, and which can detect a signal from TLR4 with expression of a reporter gene as an index.
摘要翻译：本发明提供了一种筛选用于预防或治疗选自心脏病，自身免疫疾病，炎性疾病，中枢神经系统疾病，感染性疾病，败血症，严重败血症和败血症的至少一种疾病的药物的方法其包括选择与TLR4的细胞内区域结合的物质，并抑制所述分子的信号转导，以及用于该方法的试剂盒，其包含（1）表达野生型TLR4的细胞和（2）细胞其表达突变体TLR4，并且可以以报告基因的表达作为指标检测来自TLR4的信号。

2. 发明授权

US07078540B1 Substituted aromatic-ring compounds, process for producing the same, and use 失效
公开(公告)号：US07078540B1
公开(公告)日：2006-07-18
申请号：US10048938
申请日：2000-08-03
申请人： Norikazu Tamura , Takashi Ichikawa , Masayuki Ii
发明人： Norikazu Tamura , Takashi Ichikawa , Masayuki Ii
IPC分类号： C07D315/00 , C07D321/00
CPC分类号： C07C317/44 , C07C2601/10
摘要： A compound of the formula: wherein R1 is an aliphatic hydrocarbon group optionally having substituent(s), an aromatic hydrocarbon group optionally having substituent(s), a heterocyclic group optionally having substituent(s), a group of the formula: OR1a wherein R1a is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), or a group of the formula: wherein R1b and R1c are the same or different and each is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), X is a methylene group, a nitrogen atom, a sulfur atom or an oxygen atom, Y is an optionally substituted methylene group or an optionally substituted nitrogen atom, ring A is a 5 to 8-membered ring optionally substituted further by 1 to 4 substituent(s) selected from (1) an aliphatic hydrocarbon group optionally having substituent(s), (2) an aromatic hydrocarbon group optionally having substituent(s), (3) a group of the formula: OR2 wherein R2 is a hydrogen atom, or an aliphatic hydrocarbon group optionally having substituent(s) and (4) a halogen atom, Ar is an aromatic hydrocarbon group optionally having substituent(s), a group of the formula: is a group of the formula: or the formula: m is an integer of 0 to 2, n is an integer of 1 to 3, and the sum of m and n is not more than 4, provided that when X is a methylene group, Y is an optionally substituted methylene group, and a salt thereof have an inhibitory activity on nitric oxide (NO) production and cytokine production, and are useful as an agent for the prophylaxis and/or treatment of diseases, such as cardiac disease, autoimmune disease, inflammatory disease, central nervous system disease, infectious disease, sepsis, septic shock and the like.

3. 发明授权

US07417059B2 Substituted aromatic-ring compounds, process for producing the same and use 有权
标题翻译：取代的芳环化合物，其制备方法和用途
公开(公告)号：US07417059B2
公开(公告)日：2008-08-26
申请号：US11094210
申请日：2005-03-31
申请人： Norikazu Tamura , Takashi Ichikawa , Masayuki Ii
发明人： Norikazu Tamura , Takashi Ichikawa , Masayuki Ii
IPC分类号： A61K31/44 , A61K31/38 , A61K31/35 , A61K31/235 , A61K31/34 , A61K31/18 , C07D211/00 , C07D211/08 , C07D335/02 , C07D309/00 , C07D315/00 , C07C321/00 , C07C303/00 , C07C315/00
CPC分类号： C07C317/44 , C07C2601/10
摘要： The present invention is directed to a class of cyclohexene derivatives bearing sulfamoyl and ester groups which have an inhibitory activity on nitric oxide (NO) production and cytokine production, and are useful as an agent for the prophylaxis and/or treatment of diseases such as, cardiac disease, autoimmune disease, inflammatory disease, central nervous system disease, infectious disease, sepsis, and septic shock.
摘要翻译：本发明涉及一类具有对一氧化氮（NO）产生和细胞因子产生具有抑制活性的氨磺酰基和酯基的环己烯衍生物，并且可用作预防和/或治疗疾病如心脏病，自身免疫性疾病，炎性疾病，中枢神经系统疾病，感染性疾病，败血症和败血性休克。

4. 发明申请

US20110184034A1 Severe sepsis preventive therapeutic agent 审中-公开
标题翻译：严重脓毒症预防治疗剂
公开(公告)号：US20110184034A1
公开(公告)日：2011-07-28
申请号：US13064526
申请日：2011-03-30
申请人： Masayuki Ii , Yuji Iizawa , Tomoyuki Kitazaki , Kazuki Kubo
发明人： Masayuki Ii , Yuji Iizawa , Tomoyuki Kitazaki , Kazuki Kubo
IPC分类号： A61K31/18 , A61K31/4192 , A61K31/41 , A61K31/428 , C07C311/21 , C07D249/06 , C07D257/04 , C07D275/03 , A61P31/00
CPC分类号： A61K31/4192 , A61K31/00 , A61K31/215 , A61K31/223 , A61K31/245 , A61K31/27 , A61K31/277 , A61K31/41 , A61K31/4196 , A61K31/428 , Y02A50/411
摘要： The present invention provides an agent for the prophylaxis or treatment of severe sepsis, which contains a compound represented by the formula (I): or, the formula (II): or a salt thereof or a prodrug thereof, a TLR signal inhibitor containing a non-peptide compound and an agent for the prophylaxis or treatment of organ dysfunction and the like, which contains a TLR signal inhibitory substance.
摘要翻译：本发明提供一种预防或治疗严重败血症的药剂，其含有式（I）表示的化合物或式（II）：或其盐或其前药，含有非肽化合物和用于预防或治疗器官功能障碍等的试剂，其含有TLR信号抑制物质。

5. 发明申请

US20090317833A1 Screening Method 失效
标题翻译：筛选方法
公开(公告)号：US20090317833A1
公开(公告)日：2009-12-24
申请号：US12225721
申请日：2007-03-29
申请人： Osamu Hazeki , Kaoru Hazeki , Masayuki Ii , Naoko Matsunaga
发明人： Osamu Hazeki , Kaoru Hazeki , Masayuki Ii , Naoko Matsunaga
IPC分类号： G01N33/53
CPC分类号： G01N33/566 , G01N2333/70596 , G01N2500/04 , G01N2500/10
摘要： The present invention provides a method of screening for a drug for the prophylaxis or treatment of at least one disease selected from the group consisting of cardiac disease, autoimmune disease, inflammatory disease, central nervous system disease, infectious disease, sepsis, severe sepsis and septic shock, which includes selecting a substance that binds to an intracellular region of TLR4, and inhibits signal transduction from said molecule, and a kit for this method, which contains (1) a cell that expresses wild-type TLR4 and (2) a cell that expresses a mutant TLR4, and which can detect a signal from TLR4 with expression of a reporter gene as an index.
摘要翻译：本发明提供了一种筛选用于预防或治疗选自心脏病，自身免疫疾病，炎性疾病，中枢神经系统疾病，感染性疾病，败血症，严重败血症和败血症的至少一种疾病的药物的方法其包括选择与TLR4的细胞内区域结合的物质，并抑制所述分子的信号转导，以及用于该方法的试剂盒，其包含（1）表达野生型TLR4的细胞和（2）细胞其表达突变体TLR4，并且可以以报告基因的表达作为指标检测来自TLR4的信号。

6. 发明申请

US20090105314A1 Pharmaceutical Agent 审中-公开
标题翻译：药剂
公开(公告)号：US20090105314A1
公开(公告)日：2009-04-23
申请号：US12227359
申请日：2007-05-14
申请人： Masayuki Ii , Hideyasu Matsuda , Kouji Mouri
发明人： Masayuki Ii , Hideyasu Matsuda , Kouji Mouri
IPC分类号： A61K31/24 , A61K31/4192 , A61K31/4196 , A61K31/428 , A61P9/00
CPC分类号： A61K31/215
摘要： The present invention provides an agent for the prophylaxis or treatment of complications after coronary-artery bypass surgery or cardiac diseases, autoimmune diseases, central nervous system diseases, inflammatory diseases, sepsis, severe sepsis or septic shock in a patient who undergoes coronary-artery bypass surgery, which comprises a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a compound represented by the formula (II): wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof, and an agent for the prophylaxis or treatment of sepsis and the like, as well as complications after coronary-artery bypass surgery, which is prepared for administration of ethyl (6R)-6-[(2-chloro-4-fluoroanilino)sulfonyl]-1-cyclohexene-1-carboxylate or a salt thereof or a prodrug thereof in a specific dose at a specific administration time.
摘要翻译：本发明提供了用于预防或治疗冠状动脉旁路手术后并发症的药物或心脏疾病，自身免疫性疾病，中枢神经系统疾病，炎性疾病，败血症，严重脓毒症或败血症休克的患者。手术，其包含由式（I）表示的化合物：其中每个符号如说明书中所定义，或由式（II）表示的化合物：其中每个符号如说明书中所定义，或其盐或其前药，以及用于预防或治疗败血症等的试剂以及冠状动脉搭桥手术后的并发症，其制备用于给予（6R）-6 - [（2-氯-4- 氟苯胺基）磺酰基] -1-环己烯-1-羧酸酯或其盐或其前药在特定给药时间内以特定剂量。

7. 发明申请

US20090062355A1 Pharmaceutical Product 审中-公开
标题翻译：药品
公开(公告)号：US20090062355A1
公开(公告)日：2009-03-05
申请号：US12226446
申请日：2007-04-19
申请人： Yuji Iizawa , Masayuki Ii , Tomohiro Kawamoto
发明人： Yuji Iizawa , Masayuki Ii , Tomohiro Kawamoto
IPC分类号： A61K31/428 , C07C229/46 , A61K31/215 , C07D249/04 , A61K31/4192 , A61P29/00 , A61P37/00 , C07D257/04 , A61K31/41 , C07D275/06
CPC分类号： C07D249/06 , A61K31/216 , A61K31/41 , A61K31/4192 , A61K31/428 , A61K45/06 , C07D249/08 , C07D257/04 , C07D275/06 , A61K2300/00
摘要： An agent for suppressing the production of various cytokines (IL-8 and the like) and inflammatory mediators, an agent for suppressing the expression of COX-II and the like, or an inhibitor of various phosphorylation enzymes (ATF2 and the like), which contains a TLR signaling inhibitory substance, preferably a compound represented by the formula (I) or the formula (II) wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
摘要翻译：用于抑制各种细胞因子（IL-8等）和炎性介质的产生的药剂，抑制COX-II等的表达的试剂或各种磷酸化酶（ATF2等）的抑制剂，其中含有TLR信号传导抑制物质，优选式（I）或式（II）表示的化合物，其中各符号如说明书中所定义，或其盐或其前药。

8. 发明授权

US06495604B1 Cycloalkene derivatives, process for producing the same, and use 有权
标题翻译：环烯烃衍生物，生产方法和使用
公开(公告)号：US06495604B1
公开(公告)日：2002-12-17
申请号：US09622392
申请日：2000-08-14
申请人： Yuzo Ichimori , Masayuki Ii , Katsumi Itoh , Tomoyuki Kitazaki , Junji Yamada
发明人： Yuzo Ichimori , Masayuki Ii , Katsumi Itoh , Tomoyuki Kitazaki , Junji Yamada
IPC分类号： A61K3118
CPC分类号： C07D249/08 , C07C311/14 , C07C2601/10 , C07C2601/16 , C07C2601/18 , C07D249/06 , C07D257/04 , C07D275/06
摘要： The present invention provides a compound represented by the formula: wherein R represents an aliphatic hydrocarbon group optionally having substituents, an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents, a group represented by the formula: OR1 (wherein R1 represents a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents) or a group represented by the formula: wherein R1b represents a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents, R1c is, same with or different from R1b, a hydrogen atom or an aliphatic hydrocarbon group optionally having substituents, R0 represents a hydrogen atom or an aliphatic hydrocarbon group, or R and R0 represents a bond with each other, Ar represents an aromatic hydrocarbon group optionally having substituents, and n is an integer of 1 to 4, or a salt thereof, which is a agent for preventing or treating diseases such as cardiac disease, autoimmune disease, septick shock, etc.
摘要翻译：本发明提供由下式表示的化合物：其中R表示任选具有取代基的脂族烃基，任选具有取代基的芳族烃基，任选具有取代基的杂环基，由式OR1表示的基团（其中R1表示氢原子或任选具有取代基的脂族烃基）或由下式表示的基团：其中R 1b表示氢原子或任选具有取代基的脂族烃基，R 1c与R 1b相同或不同，为氢原子或脂族任选具有取代基的烃基，R 0表示氢原子或脂族烃基，或R和R 0表示彼此的键，Ar表示任选具有取代基的芳香族烃基，n表示1〜4的整数，或者其盐，其是用于预防或治疗诸如心脏病的疾病的药剂麻疹，败血性休克等

9. 发明申请

US20120077856A1 PHARMACEUTICAL PRODUCT 审中-公开
标题翻译：药用产品
公开(公告)号：US20120077856A1
公开(公告)日：2012-03-29
申请号：US13309936
申请日：2011-12-02
申请人： Yuji IIZAWA , Masayuki Ii , Tomohiro Kawamoto
发明人： Yuji IIZAWA , Masayuki Ii , Tomohiro Kawamoto
IPC分类号： A61K31/215 , A61K31/41 , A61K31/4196 , A61K31/428 , A61P29/00 , A61P31/00 , A61P9/00 , A61P37/06 , A61P25/00 , A61P17/02 , A61P19/02 , A61P1/04 , A61P9/10 , A61P1/18 , A61P13/12 , A61P3/10 , A61P25/16 , A61P35/02 , A61P35/00 , A61P11/00 , A61P17/06 , A61K31/4192
CPC分类号： C07D249/06 , A61K31/216 , A61K31/41 , A61K31/4192 , A61K31/428 , A61K45/06 , C07D249/08 , C07D257/04 , C07D275/06 , A61K2300/00
摘要： An agent for suppressing the production of various cytokines (IL-8 and the like) and inflammatory mediators, an agent for suppressing the expression of COX-II and the like, or an inhibitor of various phosphorylation enzymes (ATF2 and the like), which contains a TLR signaling inhibitory substance, preferably a compound represented by the formula (I) or the formula (II) wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
摘要翻译：用于抑制各种细胞因子（IL-8等）和炎性介质的产生的药剂，抑制COX-II等的表达的试剂或各种磷酸化酶（ATF2等）的抑制剂，其中含有TLR信号传导抑制物质，优选式（I）或式（II）表示的化合物，其中各符号如说明书中所定义，或其盐或其前药。

10. 发明申请

US20060058288A1 Severe sepsis preventive therapeutic agent 审中-公开
标题翻译：严重脓毒症预防治疗剂
公开(公告)号：US20060058288A1
公开(公告)日：2006-03-16
申请号：US10510596
申请日：2003-04-07
申请人： Masayuki II , Yuji Iizawa , Tomoyuki Kitazaki , Kazuki Kubo
发明人： Masayuki II , Yuji Iizawa , Tomoyuki Kitazaki , Kazuki Kubo
IPC分类号： A61K31/54 , A61K31/18
CPC分类号： A61K31/4192 , A61K31/00 , A61K31/215 , A61K31/223 , A61K31/245 , A61K31/27 , A61K31/277 , A61K31/41 , A61K31/4196 , A61K31/428 , Y02A50/411
摘要： The present invention provides an agent for the prophylaxis or treatment of severe sepsis, which contains a compound represented by the formula (I): or, the formula (II): , or a salt thereof or a prodrug thereof, a TLR signal inhibitor containing a non-peptide compound and an agent for the prophylaxis or treatment of organ dysfunction and the like, which contains a TLR signal inhibitory substance.
摘要翻译：本发明提供一种预防或治疗严重败血症的药剂，其含有式（I）表示的化合物：

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