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1. 发明授权

US06410580B1 Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases 失效
标题翻译：抑制基质降解金属蛋白酶的磺酰基氨基衍生物
公开(公告)号：US06410580B1
公开(公告)日：2002-06-25
申请号：US09601462
申请日：2000-08-02
申请人： Paivi Jaana Kukkola , Leslie Ann Robinson , Junichi Sakaki , Motowo Nakajima
发明人： Paivi Jaana Kukkola , Leslie Ann Robinson , Junichi Sakaki , Motowo Nakajima
IPC分类号： C07D27506
CPC分类号： C07D417/12 , C07C311/19 , C07D233/74 , C07D239/96 , C07D275/06 , C07D417/14 , C07D471/04
摘要： Compounds of formula (I) wherein W is —OH or —NHOH; X is an optionally substituted heterocycle, NR1SO2R2, heterocyclylalkythio, CONR2R3 or NR1COR2; Y, Z, R1-R3 and n are as defined in the application. Compounds (I) are inhibitors of matrix-degrading metalloproteinases and are use for the treatment of related conditions.
摘要翻译：其中W是-OH或-NHOH的式（I）化合物; X是任选取代的杂环，NR 1 SO 2 R 2，杂环基炔基，CONR 2 R 3或NR 1 COR 2; Y，Z，R 1 -R 3和n如本申请中所定义。化合物（I）是基质降解金属蛋白酶的抑制剂，用于治疗相关病症。

2. 发明授权

US06277987B1 Sulfonylamino acid and sulfonylamino hydroxamic acid derivatives 失效
标题翻译：磺酰氨基酸和磺酰氨基异羟肟酸衍生物
公开(公告)号：US06277987B1
公开(公告)日：2001-08-21
申请号：US09243854
申请日：1999-02-03
申请人： Paivi Jaana Kukkola , Leslie Anne Robinson , Motowo Nakajima , Junichi Sakaki
发明人： Paivi Jaana Kukkola , Leslie Anne Robinson , Motowo Nakajima , Junichi Sakaki
IPC分类号： C07D23972
CPC分类号： C07D417/12 , C07C311/19 , C07D233/74 , C07D239/96 , C07D275/06 , C07D417/14 , C07D471/04
摘要： Compounds of formula wherein W is —OH or —NHOH; X is a heterocycle with the proviso that when X is a nitrogen containing heterocycle, the heterocycle is attached to the (CH2)m moiety by a ring nitrogen, —CONR2R3, —NR1COR2, —NR1SO2R2, —NR1CONR2R3, —NR1COOR4, heteroarylthio, alkylthio, arylalkylthio, heteroarylalkylthio, heterocycloalkylalkylthio, heterocycloalkylthio or arylthio; Y is carbon, nitrogen, oxygen or sulfur, provided that when Y is carbon, n is 2; Z is alkyl, aryl, alkoxy, aryloxy, aralkoxyaryl, aralkoxyheteroaryl, heteroaryl, heterocycloalkyl, heteroaryloxy, —CONR2R3, —NR1COR2, —NR1CONR2R3, —OCONR2R3, —NR1COOR4, or —SO2R2; R1 is hydrogen, alkyl, heterocycloalkylalkyl, aralkyl or heteroarylalkyl; R2 and R3 are independently R1, aryl or heteroaryl; or R2 and R3 taken together with the nitrogen atom to which they are attached form a 5- to 7-membered ring, which may optionally contain another heteroatom selected from oxygen, nitrogen and sulfur; R4 is alkyl, heterocycloalkylalkyl, aralkyl, aryl or heteroaryl; m represents an integer from one to six; n represents the integer one or two; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; and a method of inhibiting matrix-degrading metalloproteinases in mammals using such compounds. Compounds of formula I are inhibitors of matrix-degrading metalloproteinases and are useful for the treatment of conditions related thereto.
摘要翻译：肟基的化合物W是-OH或-NHOH; X是杂环，条件是当X是含氮杂环时，杂环通过环氮-CONR2R3，-NR1COR2，-NR1SO2R2与（CH2）m部分连接，-NR 1 CONR 2 R 3，-NR 1 COOR 4，杂芳硫基，烷硫基，芳烷硫基，杂芳基烷硫基，杂环烷基烷硫基，杂环烷硫基或芳硫基; Y为碳，氮，氧或硫，条件是当Y为碳时，n为2; Z为烷基，芳基，烷氧基，芳氧基，芳烷氧基芳基，芳烷氧基杂芳基，杂芳基，杂环烷基，杂芳氧基，-CONR2R3，-NR1COR2，-NR1CONR2R3，-OCONR2R3，-NR1COOR4或-SO2R2; R1是氢，烷基，杂环烷基烷基，芳烷基或杂芳基烷基; R2和R3独立地是R1，芳基或杂芳基; 或者R 2和R 3与它们所连接的氮原子一起形成5-至7-元环，其可任选地含有选自氧，氮和硫的其它杂原子; R 4是烷基，杂环烷基烷基，芳烷基，芳基或杂芳基 ; m表示1至6的整数; n表示整数1或2; 及其药学上可接受的盐; 包含所述化合物的药物组合物; 以及使用这些化合物抑制哺乳动物中的基质降解金属蛋白酶的方法。式I化合物是基质降解金属蛋白酶的抑制剂，可用于治疗与之相关的病症。

3. 发明授权

US08034810B2 Arylsulfonamido-substituted hydroxamic acid derivatives 失效
标题翻译：芳基磺酰氨基取代的异羟肟酸衍生物
公开(公告)号：US08034810B2
公开(公告)日：2011-10-11
申请号：US11581524
申请日：2006-10-16
申请人： Werner Breitenstein , Kenji Hayakawa , Genji Iwasaki , Takanori Kanazawa , Tatsuhiko Kasaoka , Shinichi Koizumi , Shinichiro Matsunaga , Motowo Nakajima , Junichi Sakaki
发明人： Werner Breitenstein , Kenji Hayakawa , Genji Iwasaki , Takanori Kanazawa , Tatsuhiko Kasaoka , Shinichi Koizumi , Shinichiro Matsunaga , Motowo Nakajima , Junichi Sakaki
IPC分类号： A61K31/535 , C07D211/70
CPC分类号： C07D207/32 , C07C311/29 , C07D213/42 , C07D215/12 , C07D231/12 , C07D233/56 , C07D233/64 , C07D249/06 , C07D249/08 , C07D257/04 , C07D295/125 , C07D295/13 , C07D295/135 , C07D307/52 , C07D333/20
摘要： α-Amino hydroxamic acid derivative of the formula I, in which R is C2-C7-alkyl, which is mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C3-C5-cycloalkyl or unsubstituted or substituted C3-C6-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; or C3-C7-alkenyl or C3-C7-alkynyl, which in each case is unsubstituted or mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C3-C5-cycloalkyl or unsubstituted or substituted C3-C6-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; and the other symbols are as defined in claim 1, are described. These compounds are MMP and in particular MMP2 inhibitors and can be used for treatment of MMP dependent diseases, in particular inflammation conditions, rheumatoid arthritis, osteoarthritis, tumors (tumor growth, metastasis, progression or invasion) and pulmonary disorders (e.g. emphysema, COPD).
摘要翻译：式I的α-氨基异羟肟酸衍生物，其中R是C 2 -C 7 - 烷基，其被卤素，硝基，低级酰氧基，三氟甲氧基，氰基，C 3 -C 5 - 环烷基或未取代的单或二取代或二取代或三取代，包含一个或两个选自O，S和N的杂原子的取代的C3-C6-杂芳基; 或C 3 -C 7 - 烯基或C 3 -C 7 - 炔基，其在每种情况下是未取代的或被卤素，硝基，低级酰氧基，三氟甲氧基，氰基，C 3 -C 5 - 环烷基或未取代或取代的C3- 包含一个或两个选自O，S和N的杂原子的C 6 - 杂芳基; 并且其它符号如权利要求1中所定义。这些化合物是MMP，特别是MMP2抑制剂，可用于治疗MMP依赖性疾病，特别是炎症病症，类风湿性关节炎，骨关节炎，肿瘤（肿瘤生长，转移，进展或侵袭）和肺部疾病（例如肺气肿，COPD）。

4. 发明申请

US20080275127A1 Arylsulfonamido-substituted hydroxamic acid derivatives 失效
标题翻译：芳基磺酰氨基取代的异羟肟酸衍生物
公开(公告)号：US20080275127A1
公开(公告)日：2008-11-06
申请号：US11581524
申请日：2006-10-16
申请人： Werner Breitenstein , Kenji Hayakawa , Genji Iwasaki , Takanori Kanazawa , Tatsuhiko Kasaoka , Shinichi Koizumi , Shinichiro Matsunaga , Motowo Nakajima , Junichi Sakaki
发明人： Werner Breitenstein , Kenji Hayakawa , Genji Iwasaki , Takanori Kanazawa , Tatsuhiko Kasaoka , Shinichi Koizumi , Shinichiro Matsunaga , Motowo Nakajima , Junichi Sakaki
IPC分类号： A61K31/18 , C07C303/00
CPC分类号： C07D207/32 , C07C311/29 , C07D213/42 , C07D215/12 , C07D231/12 , C07D233/56 , C07D233/64 , C07D249/06 , C07D249/08 , C07D257/04 , C07D295/125 , C07D295/13 , C07D295/135 , C07D307/52 , C07D333/20
摘要： α-Amino hydroxamic acid derivative of the formula I, in which R is C2-C7-alkyl, which is mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C3-C5-cycloalkyl or unsubstituted or substituted C3-C6-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; or C3-C7-alkenyl or C3-C7-alkynyl, which in each case is unsubstituted or mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C3-C5-cycloalkyl or unsubstituted or substituted C3-C6-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; and the other symbols are as defined in claim 1, are described. These compounds are MMP and in particular MMP2 inhibitors and can be used for treatment of MMP dependent diseases, in particular inflammation conditions, rheumatoid arthritis, osteoarthritis, tumors (tumor growth, metastasis, progression or invasion) and pulmonary disorders (e.g. emphysema, COPD).
摘要翻译：式I的α-氨基异羟肟酸衍生物，其中R是C 2 -C 7 - 烷基，其被卤素，硝基的单，二或三取代，低级酰氧基，三氟甲氧基，氰基，C 3 -C 5 - 环烷基或未取代或取代的C 3 -C 6 - 包含一个或两个选自O，S和N的杂原子的杂芳基; 或C 3 -C 7 - 烯基或C 3 -C 7 - 炔基，其在每种情况下为未取代的或被卤素，硝基，低级酰氧基，三氟甲氧基，氰基，C 3 -C 5 - 环烷基或未取代或取代的C 1 - 3个-C 6 -C 6 - 杂芳基，其包含一个或两个选自O，S和N的杂原子; 并且其它符号如权利要求1中所定义。这些化合物是MMP，特别是MMP2抑制剂，可用于治疗MMP依赖性疾病，特别是炎症病症，类风湿性关节炎，骨关节炎，肿瘤（肿瘤生长，转移，进展或侵袭）和肺部疾病（例如肺气肿，COPD）。

5. 发明授权

US07138432B1 Arylsulfonamido-substituted hydroxamic acid derivatives 失效
标题翻译：芳基磺酰氨基取代的异羟肟酸衍生物
公开(公告)号：US07138432B1
公开(公告)日：2006-11-21
申请号：US10048932
申请日：2000-08-07
申请人： Werner Breitenstein , Kenji Hayakawa , Genji Iwasaki , Takanori Kanazawa , Tatsuhiko Kasaoka , Shinichi Koizumi , Shinichiro Matsunaga , Motowo Nakajima , Junichi Sakaki
发明人： Werner Breitenstein , Kenji Hayakawa , Genji Iwasaki , Takanori Kanazawa , Tatsuhiko Kasaoka , Shinichi Koizumi , Shinichiro Matsunaga , Motowo Nakajima , Junichi Sakaki
IPC分类号： A61K31/18 , C07C303/00
CPC分类号： C07D207/32 , C07C311/29 , C07D213/42 , C07D215/12 , C07D231/12 , C07D233/56 , C07D233/64 , C07D249/06 , C07D249/08 , C07D257/04 , C07D295/125 , C07D295/13 , C07D295/135 , C07D307/52 , C07D333/20
摘要： α-Amino hydroxamic acid derivative of formula (I), in which R is C2–C7-alkyl, which is mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C3–C5-cycloalkyl or unsubstituted or substituted C3–C4-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; or C3–C7-alkenyl or C3–C7-alkynyl, which in each case is unsubstituted or mono-, di- or trisubstituted by halogen, nitro, lower acyloxy, trifluoromethoxy, cyano, C3–C5-cycloalkyl or unsubstituted or substituted C3–C6-heteroaryl comprising one or two heteroatoms selected from the group consisting of O, S and N; and the other symbols are as defined in claim 1, are described. These compounds are MMP and in particular MMP2 inhibitors and can be used for treatment of MMP dependent diseases, in particular inflammation conditions, rheumatoid arthritis, osteoarthritis, tumors (tumor growth, metastasis, progression or invasi n) and pulmonary disorders (e.g. emphysema, COPD).
摘要翻译：式（I）的α-氨基异羟肟酸衍生物，其中R为C 2 -C 7 -C 7 - 烷基，其被卤素单，二或三取代，硝基，低级酰氧基，三氟甲氧基，氰基，C 3 -C 5 - 环烷基或未取代或取代的C 3 -C 4 - 包含一个或两个选自O，S和N的杂原子的杂芳基; 或C 3 -C 7 - 烯基或C 3 -C 7 - 炔基，其在每种情况下为未取代的或被卤素，硝基，低级酰氧基，三氟甲氧基，氰基，C 3 -C 5 - 环烷基或未取代或取代的C 1 - 3个-C 6 -C 6 - 杂芳基，其包含一个或两个选自O，S和N的杂原子; 并且其它符号如权利要求1中所定义。这些化合物是MMP，特别是MMP2抑制剂，可用于治疗MMP依赖性疾病，特别是炎症病症，类风湿性关节炎，骨关节炎，肿瘤（肿瘤生长，转移，进展或侵袭性）和肺部疾病（例如肺气肿，COPD ）。

6. 发明申请

US20140249217A1 ENHANCER OF SURVIVAL OF TRANSPLANTED ORGAN 有权
标题翻译：运输机构存货增值
公开(公告)号：US20140249217A1
公开(公告)日：2014-09-04
申请号：US14350488
申请日：2012-09-12
申请人： Ko Rii , Kiwamu Takahashi , Naomi Haga , Fuminori Abe , Tohru Tanaka , Motowo Nakajima , Hidenori Ito
发明人： Ko Rii , Kiwamu Takahashi , Naomi Haga , Fuminori Abe , Tohru Tanaka , Motowo Nakajima , Hidenori Ito
IPC分类号： A61K31/197 , A61K31/295
CPC分类号： A61K31/197 , A01N1/0226 , A61K31/22 , A61K31/295 , A61K33/26 , A61K35/17 , A61K45/06 , A61K2035/122 , A61K2035/124 , A61K2300/00
摘要： The present invention provides an agent for promoting graft survival which can suppress rejection without use of existing immunosuppressants, an organ preservation solution capable of maintaining the freshness of an organ excised from a donor, and the like. An agent for promoting graft survival or an organ preservation solution is prepared, which comprises 5-aminolevulinic acid (ALA) or a derivative thereof, or a salt of ALA or the derivative and an iron compound as active ingredients. Preferable examples of the ALAs can include ALA and various esters such as methyl ester, ethyl ester, propyl ester, butyl ester, and pentyl ester of ALA, and their hydrochlorides, phosphates, and sulfates. Preferable examples of the iron compound can include sodium ferrous citrate.
摘要翻译：本发明提供了一种用于促进移植物存活的药剂，其可以抑制不使用现有的免疫抑制剂的排斥反应，能够保持从供体排出的器官的新鲜度的器官保存溶液等。制备促进移植物存活的药物或器官保存溶液，其包含5-氨基乙酰丙酸（ALA）或其衍生物，或ALA或其衍生物和铁化合物的盐作为活性成分。 ALA的优选实例可以包括ALA和各种酯，例如ALA的甲酯，乙酯，丙酯，丁酯和戊酯，以及它们的盐酸盐，磷酸盐和硫酸盐。铁化合物的优选实例可包括柠檬酸亚铁钠。

7. 发明申请

US20120277246A1 Use of N-Phenyl-2-pyrimidineamine Derivatives Against Mast Cell-based Diseases Like Allergic Disorders 审中-公开
标题翻译：使用N-苯基-2-嘧啶胺衍生物对抗基于细胞的疾病如过敏性疾病
公开(公告)号：US20120277246A1
公开(公告)日：2012-11-01
申请号：US13523198
申请日：2012-06-14
申请人： Michael Heinrich , Kenichi Koike , Atsushi Komiyama , Motowo Nakajima , Kouichi Takeuchi
发明人： Michael Heinrich , Kenichi Koike , Atsushi Komiyama , Motowo Nakajima , Kouichi Takeuchi
IPC分类号： A61K31/506 , A61P35/00
CPC分类号： A61K31/506
摘要： Use of the N-phenyl-2-pyrimidine-amine derivatives of formula I, in which the symbols and substituents have the meaning as given herein in free form or in pharmaceutically acceptable salt form in the manufacture of a pharmaceutical composition for the treatment of allergic rhinitis, allergic dermatitis, drug allergy or food allergy, angioedema, urticaria, sudden infant death syndrome, bronchopulmonary aspergillosis, multiple sclerosis or mastocytosis;
摘要翻译：使用式I的N-苯基-2-嘧啶 - 胺衍生物，其中符号和取代基具有本文给出的含义，以游离形式或药学上可接受的盐形式用于制备用于治疗过敏性的药物组合物鼻炎，过敏性皮炎，药物过敏或食物过敏，血管性水肿，荨麻疹，婴儿猝死综合征，支气管肺曲霉病，多发性硬化或肥大细胞增多症;

8. 发明申请

US20110201619A1 Use of N-Phenyl-2-pyrimidineamine Derivatives Against Mast Cell-based Diseases Like Allergic Disorders 审中-公开
标题翻译：使用N-苯基-2-嘧啶胺衍生物对抗基于细胞的疾病如过敏性疾病
公开(公告)号：US20110201619A1
公开(公告)日：2011-08-18
申请号：US13090752
申请日：2011-04-20
申请人： Michael Heinrich , Kenichi Koike , Atsushi Komiyama , Motowo Nakajima , Kouichi Takeuchi
发明人： Michael Heinrich , Kenichi Koike , Atsushi Komiyama , Motowo Nakajima , Kouichi Takeuchi
IPC分类号： A61K31/506 , C07D401/14 , A61P17/00 , A61P35/00 , A61P37/08
CPC分类号： A61K31/506
摘要： Use of the N-phenyl-2-pyrimidine-amine derivatives of formula I, in which the symbols and substituents have the meaning as given herein in free form or in pharmaceutically acceptable salt form in the manufacture of a pharmaceutical composition for the treatment of allergic rhinitis, allergic dermatitis, drug allergy or food allergy, angioedema, urticaria, sudden infant death syndrome, bronchopulmonary aspergillosis, multiple sclerosis or mastocytosis;
摘要翻译：使用式I的N-苯基-2-嘧啶 - 胺衍生物，其中符号和取代基具有本文给出的含义，以游离形式或药学上可接受的盐形式用于制备用于治疗过敏性的药物组合物鼻炎，过敏性皮炎，药物过敏或食物过敏，血管性水肿，荨麻疹，婴儿猝死综合征，支气管肺曲霉病，多发性硬化或肥大细胞增多症;

9. 发明申请

US20100144750A1 Use of N-Phenyl-2-Pyrimidineamine Derivatives Against Mast Cell-Based Diseases Like Allergic Disorders 审中-公开
标题翻译：使用N-苯基-2-嘧啶胺衍生物对抗肥大细胞性疾病如过敏性疾病
公开(公告)号：US20100144750A1
公开(公告)日：2010-06-10
申请号：US12687544
申请日：2010-01-14
申请人： Michael Heinrich , Kenichi Koike , Atsushi Komiyama , Motowo Nakajima , Kouichi Takeuchi
发明人： Michael Heinrich , Kenichi Koike , Atsushi Komiyama , Motowo Nakajima , Kouichi Takeuchi
IPC分类号： A61K31/506 , A61P35/00 , A61P17/00 , A61P11/02 , A61P37/08 , A61P25/28
CPC分类号： A61K31/506
摘要： Use of the N-phenyl-2-pyrimidine-amine derivatives of formula I, in which the symbols and substituents have the meaning as given herein in free form or in pharmaceutically acceptable salt form in the manufacture of a pharmaceutical composition for the treatment of allergic rhinitis, allergic dermatitis, drug allergy or food allergy, angioedema, urticaria, sudden infant death syndrome, bronchopulmonary aspergillosis, multiple sclerosis or mastocytosis;
摘要翻译：使用式I的N-苯基-2-嘧啶 - 胺衍生物，其中符号和取代基具有本文给出的含义，以游离形式或药学上可接受的盐形式用于制备用于治疗过敏性的药物组合物鼻炎，过敏性皮炎，药物过敏或食物过敏，血管性水肿，荨麻疹，婴儿猝死综合征，支气管肺曲霉病，多发性硬化或肥大细胞增多症;

10. 发明授权

US09314443B2 Enhancer of survival of transplanted organ 有权
标题翻译：移植器官生存增强
公开(公告)号：US09314443B2
公开(公告)日：2016-04-19
申请号：US14350488
申请日：2012-09-12
申请人： Ko Rii , Kiwamu Takahashi , Naomi Haga , Fuminori Abe , Tohru Tanaka , Motowo Nakajima , Hidenori Ito
发明人： Ko Rii , Kiwamu Takahashi , Naomi Haga , Fuminori Abe , Tohru Tanaka , Motowo Nakajima , Hidenori Ito
IPC分类号： A61K31/195 , A61K31/265 , A61K31/197 , A61K33/26 , A61K31/22 , A61K31/295 , A61K45/06
CPC分类号： A61K31/197 , A01N1/0226 , A61K31/22 , A61K31/295 , A61K33/26 , A61K35/17 , A61K45/06 , A61K2035/122 , A61K2035/124 , A61K2300/00
摘要： The present invention provides an agent for promoting graft survival which can suppress rejection without use of existing immunosuppressants, an organ preservation solution capable of maintaining the freshness of an organ excised from a donor, and the like. An agent for promoting graft survival or an organ preservation solution is prepared, which comprises 5-aminolevulinic acid (ALA) or a derivative thereof, or a salt of ALA or the derivative and an iron compound as active ingredients. Preferable examples of the ALAs can include ALA and various esters such as methyl ester, ethyl ester, propyl ester, butyl ester, and pentyl ester of ALA, and their hydrochlorides, phosphates, and sulfates. Preferable examples of the iron compound can include sodium ferrous citrate.
摘要翻译：本发明提供了一种用于促进移植物存活的药剂，其可以抑制不使用现有的免疫抑制剂的排斥反应，能够保持从供体排出的器官的新鲜度的器官保存溶液等。制备促进移植物存活的药剂或器官保存溶液，其包含5-氨基乙酰丙酸（ALA）或其衍生物，或ALA或其衍生物和铁化合物的盐作为活性成分。 ALA的优选实例可以包括ALA和各种酯，例如ALA的甲酯，乙酯，丙酯，丁酯和戊酯，以及它们的盐酸盐，磷酸盐和硫酸盐。铁化合物的优选实例可包括柠檬酸亚铁钠。

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