公开(公告)号：US08227502B2

公开(公告)日：2012-07-24

申请号：US12514634

申请日：2007-11-09

申请人： Torbjorn Lundstedt ,  Elisabeth Seifert ,  Per Lek ,  Arne Boman

发明人： Torbjorn Lundstedt ,  Elisabeth Seifert ,  Per Lek ,  Arne Boman

IPC分类号： A61K31/404 ,  C07D209/14

CPC分类号： C07D209/14

摘要： There are described Compounds of formula (I) in which R3 to R8 are independently selected from hydrogen, halogen, trihaloalkyl, alkyl having 1, 2, 3, 4 or 5 carbon atoms, electron donor groups selected from alkoxy having 1, 2, 3, 4 or 5 carbon atoms, trihaloalkoxy, hydroxy or amino, electron acceptor groups selected from cyano, sulphonic, nitro, or amide; R1 is an optionally substituted phenyl, benzyl or cyclohexyl group; R2 is selected from amino, substituted amino or guanidino groups, Z is a saturated or unsaturated C1-5 hydrocarbon chain, and salts thereof. A process for their preparation and compositions containing them are also described. The Compounds are either agonists or antagonists of a specific adenosine receptor or a number of adenosine receptors and have usefulness for the treatment of inflammation, arthritic conditions, rheumatoid arthritis, osteoarthritis, mental disorders, or for inducing central nerve regeneration.

摘要翻译： 描述了其中R 3至R 8独立地选自氢，卤素，三卤代烷基，具有1,2,3,4或5个碳原子的烷基的式（I）化合物，选自具有1,2,3或4个碳原子的烷氧基的电子给体基团 4或5个碳原子，三卤代烷氧基，羟基或氨基，选自氰基，磺酸，硝基或酰胺的电子受体基团; R1是任选取代的苯基，苄基或环己基; R2选自氨基，取代的氨基或胍基，Z是饱和或不饱和的C 1-5烃链及其盐。 还描述了其制备方法和含有它们的组合物。 化合物是特定腺苷受体的激动剂或拮抗剂或多种腺苷受体，并且可用于治疗炎症，关节炎病症，类风湿性关节炎，骨关节炎，精神障碍或用于诱导中枢神经再生。

公开(公告)号：US08148429B2

公开(公告)日：2012-04-03

申请号：US11639190

申请日：2006-12-15

申请人： Torbjörn Lundstedt ,  Anna Skottner ,  Elisabeth Seifert

发明人： Torbjörn Lundstedt ,  Anna Skottner ,  Elisabeth Seifert

IPC分类号： A61K31/155 ,  A01N37/52 ,  A01N37/30

CPC分类号： C07C281/16 ,  A61K31/155 ,  C07C53/10 ,  C07C309/30 ,  C07C309/46 ,  C07D317/58

摘要： The present invention relates to the use of compounds of general formula (I) as ligands to the melanocortin receptors and/or for treatment of disorders in the melanocortin system: wherein X is H or OH; R1, R2, R3, R4 and R5 are the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide; alkylamino, benzoyloxy, nitroxy, phenyl or sulpho; and the pharmacologically active salts thereof.

摘要翻译： 本发明涉及通式（I）的化合物作为黑皮质素受体的配体和/或用于治疗黑皮质素系统中的病症的用途：其中X是H或OH; R 1，R 2，R 3，R 4和R 5相同或不同，选自氢，卤素，具有1-5个碳原子的烷基，电子给体基团如具有1-5个碳原子的烷氧基或羟基，电子受体基团 氰基，硝基，三氟烷基或酰胺; 烷基氨基，苯甲酰氧基，硝酰基，苯基或磺基; 及其药理学活性盐。

公开(公告)号：US10544103B2

公开(公告)日：2020-01-28

申请号：US15737125

申请日：2016-06-22

申请人： ANAMAR AB

发明人： Lars Pettersson

IPC分类号： C07D231/06 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D409/04 ,  C07D231/54 ,  A61P29/00

摘要： Provided are 1-amidino-3-aryl-2-pyrazoline derivatives which exhibit antagonizing activity towards serotonin 5-HT 2B receptors and pharmaceutical compositions containing these derivatives. Also provided is the use of the compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases.

公开(公告)号：US09227927B2

公开(公告)日：2016-01-05

申请号：US13803555

申请日：2013-03-14

申请人： AnaMar AB

发明人： Torbjorn Lundstedt ,  Anna Skottner ,  Elisabeth Seifert

IPC分类号： C07C281/16 ,  A61K31/155 ,  C07C55/10 ,  C07C309/30 ,  C07C309/40 ,  C07D317/58 ,  C07C53/10 ,  C07C309/46

CPC分类号： C07C281/16 ,  A61K31/155 ,  C07C53/10 ,  C07C309/30 ,  C07C309/46 ,  C07D317/58

摘要： The present invention relates to the use of compounds of general formula (I) as ligands to the melanocortin receptors and/or for treatment of disorders in the melanocortin system: wherein X is H or OH; R1, R2, R3, R4 and R5 are the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide; alkylamino, benzoyloxy, nitroxy, phenyl or sulpho; and the pharmacologically active salts thereof.

摘要翻译： 本发明涉及通式（I）的化合物作为黑皮质素受体的配体和/或用于治疗黑皮质素系统中的病症的用途：其中X是H或OH; R 1，R 2，R 3，R 4和R 5相同或不同，选自氢，卤素，具有1-5个碳原子的烷基，电子给体基团如具有1-5个碳原子的烷氧基或羟基，电子受体基团 氰基，硝基，三氟烷基或酰胺; 烷基氨基，苯甲酰氧基，硝酰基，苯基或磺基; 及其药理学活性盐。

公开(公告)号：US08663944B2

公开(公告)日：2014-03-04

申请号：US12806590

申请日：2010-08-17

申请人： Pilar Lorenzo ,  Tore Saxne ,  Dick Heineg{dot over (a)}rd

发明人： Pilar Lorenzo ,  Tore Saxne ,  Dick Heineg{dot over (a)}rd

IPC分类号： G01N33/00

CPC分类号： G01N33/6893 ,  C07K14/78 ,  C07K16/18 ,  G01N2800/102 ,  G01N2800/105

摘要： A method for differentiation of osteoarthritis from rheumatoid arthritis and non-disease conditions in a sample, comprising measuring in the sample the concentration of human cartilage intermediate layer protein 2 (CILP-2) in body fluids and more specifically, measuring in the sample the concentration of the N-terminal part of CILP-2 (2C1) or fragments thereof.

摘要翻译： 一种在样品中分化类风湿关节炎和非疾病状况的骨关节炎的方法，包括在样品中测量体液中人软骨中间层蛋白2（CILP-2）的浓度，更具体地，在样品中测量浓度 的CILP-2（2C1）的N-末端部分或其片段。

公开(公告)号：US08580529B2

公开(公告)日：2013-11-12

申请号：US12928884

申请日：2010-12-22

申请人： Mikael Danfelter ,  Patrik Önnerfjord ,  Dick Heinegård

发明人： Mikael Danfelter ,  Patrik Önnerfjord ,  Dick Heinegård

IPC分类号： G01N31/00 ,  G01N33/53

CPC分类号： G01N33/6887 ,  C07K14/78 ,  G01N2333/78 ,  G01N2800/10

摘要： A method for detecting or monitoring the presence of protein fragments, cleaved at novel cleaving sites near the N-terminal part of the collagen IX alpha 1 chain, close to the C-terminal part of the NC4 domain, and at the COL3 domain close to the NC3 domain. Neoepitope antibodies against the neoepitopes were created by the cleavages and an epitope in the cleaved N-terminal part of the NC4 domain unique to collagen IX. A diagnostic kit and antibodies useful in carrying out such methods are also presented.

摘要翻译： 用于检测或监测蛋白质片段的存在的方法，其在胶原IXα1链的N末端附近的接近NC4结构域的C末端部分附近的切割位点和接近于 NC3域。 通过切割和在胶原IX独特的NC4结构域的切割的N-末端部分中的表位产生针对新表皮的Neoepitope抗体。 还提供了诊断试剂盒和用于实施这些方法的抗体。

公开(公告)号：US08372878B2

公开(公告)日：2013-02-12

申请号：US12518335

申请日：2007-12-13

申请人： Torbjorn Lundstedt ,  Elisabeth Seifert ,  Per Lek ,  Arne Boman

发明人： Torbjorn Lundstedt ,  Elisabeth Seifert ,  Per Lek ,  Arne Boman

IPC分类号： A61K31/38 ,  C07D339/00

CPC分类号： C07D339/08 ,  C07C281/18 ,  C07C323/48

摘要： There are described compounds of general formula (I) and isomeric forms thereof wherein n is 0, 1, 2 or 3, saturated or unsaturated; most preferably at least one of R1 to R5 represents halogen; at least one of R1, R2, R3, R4 and R5 is selected from —S—R or —COOR, or two or more Of R1-R5 comprise a linking group such as —S—(CH2)mS—, where m is 1, 2 or 3 and R is selected from alkyl having 1 to 5 carbon atoms, cycloalkyl having 3-6 carbon atoms, hydroxy, and aryl having 6 to 10 carbon atoms, such groups being optionally substituted, and when R1 is selected from —S—R, then at least one of R2, R3 and R5 is most preferably selected from halogen; and R1, R2, R3, R4 and R5 are otherwise the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide; alkylamino, benzoyloxy, nitroxy, phenyl or sulpho; and pharmacologically acceptable salts thereof. Compounds described have activity on the melanocortin receptors and have application in the treatment of a wide range of inflammatory, arthritic or central nerve regeneration conditions.

摘要翻译： 描述了通式（I）的化合物及其异构体形式，其中n为0,1,2或3，饱和或不饱和; 最优选R 1至R 5中的至少一个表示卤素; R 1，R 2，R 3，R 4和R 5中的至少一个选自-S-R或-COOR，或者R 1 -R 5中的两个或多个包含连接基团，例如-S-（CH 2）m S-，其中m是 1,2或3，并且R选自具有1至5个碳原子的烷基，具有3-6个碳原子的环烷基，羟基和具有6至10个碳原子的芳基，这些基团任选被取代，并且当R 1选自 - S-R，则R 2，R 3和R 5中的至少一个最优选选自卤素; R 1，R 2，R 3，R 4和R 5相同或不同，选自氢，卤素，具有1至5个碳原子的烷基，电子给体基团如具有1-5个碳原子的烷氧基或羟基，电子受体基团 选自氰基，硝基，三氟烷基或酰胺; 烷基氨基，苯甲酰氧基，硝酰基，苯基或磺基; 及其药理学上可接受的盐。 所描述的化合物对黑皮质素受体具有活性，并且可用于治疗广泛的炎性，关节炎或中枢神经再生条件。

公开(公告)号：US08110663B2

公开(公告)日：2012-02-07

申请号：US12768614

申请日：2010-04-27

申请人： Dick Heinegård

发明人： Dick Heinegård

IPC分类号： G01N33/533

CPC分类号： G01N33/6887

摘要： The present invention provides a new sensitive direct sandwich assay for determining the presence of COMP in a clinical sample. Two monoclonal antibodies directed against separate antigenic determinants of the COMP molecules are used in the assay. The invention also relates to three particularly advantageous monoclonal antibodies per se that are directed against human COMP. Cell cultures manufacturing these antibodies have been deposited according to the Budapest Treaty at Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH, and have been assigned accesion numbers DSM ACC2406, DSM ACC2408 and DSM ACC2418, respectively. A diagnostic kit comprising at least two of these monoclonal antibodies also constitute a part of the present invention.

摘要翻译： 本发明提供用于确定临床样品中COMP的存在的新的敏感直接夹心测定法。 在测定中使用针对COMP分子的分离的抗原决定簇的两种单克隆抗体。 本发明还涉及针对人COMP的三种特别有利的单克隆抗体本身。 制造这些抗体的细胞培养物已经根据布达佩斯条约在Deutsche Sammlung von Mikroorganismen和Zellkulturen GmbH进行保藏，并分别被分配到DSM ACC2406，DSM ACC2408和DSM ACC2418。 包含这些单克隆抗体中的至少两种的诊断试剂盒也构成本发明的一部分。

公开(公告)号：US20220267268A1

公开(公告)日：2022-08-25

申请号：US17619359

申请日：2020-06-16

申请人： Anamar AB

发明人： Lars Pettersson

IPC分类号： C07D209/60 ,  A61K31/403 ,  A61K45/06 ,  A61K31/437 ,  C07D471/04 ,  A61P17/00

摘要： The present invention relates to tricyclic 1-amidino-4-methyl-[2,3 fused]-2-pyrroline derivatives of the general formula (I). The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, inflammatory diseases, and cancer, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.

公开(公告)号：US08410174B2

公开(公告)日：2013-04-02

申请号：US13426096

申请日：2012-03-21

申请人： Torbjörn Lundstedt ,  Anna Skottner ,  Elisabeth Seifert

发明人： Torbjörn Lundstedt ,  Anna Skottner ,  Elisabeth Seifert

IPC分类号： A61K31/155 ,  A01N37/52 ,  A01N37/30

CPC分类号： C07C281/16 ,  A61K31/155 ,  C07C53/10 ,  C07C309/30 ,  C07C309/46 ,  C07D317/58

摘要： The present invention relates to the use of compounds of general formula (I) as ligands to the melanocortin receptors and/or for treatment of disorders in the melanocortin system: wherein X is H or OH; R1, R2, R3, R4 and R5 are the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide; alkylamino, benzoyloxy, nitroxy, phenyl or sulpho; and the pharmacologically active salts thereof.

摘要翻译： 本发明涉及通式（I）的化合物作为黑皮质素受体的配体和/或用于治疗黑皮质素系统中的病症的用途：其中X是H或OH; R 1，R 2，R 3，R 4和R 5相同或不同，选自氢，卤素，具有1-5个碳原子的烷基，电子给体基团如具有1-5个碳原子的烷氧基或羟基，电子受体基团 氰基，硝基，三氟烷基或酰胺; 烷基氨基，苯甲酰氧基，硝酰基，苯基或磺基; 及其药理学活性盐。