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1. 发明授权

US08455515B2 Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, pharmaceutical compositions and therapeutic use 有权
标题翻译：取代的4-苯基四氢异喹啉，其制备方法，药物组合物和治疗用途
公开(公告)号：US08455515B2
公开(公告)日：2013-06-04
申请号：US12046928
申请日：2008-03-12
申请人： Hans-Jochen Lang
发明人： Hans-Jochen Lang
IPC分类号： C07D217/04 , A61K31/472
CPC分类号： C07D217/14
摘要： The present invention relates to substituted 4-phenyltetrahydroisoquinoline compounds and pharmaceutical compositions comprising them which are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular of the sodium-hydrogen exchanger of subtype 3 (NHE-3). As such these compounds are useful in the treatment of various disorders of the renal and respiratory systems such as acute or chronic renal failure, pulmonary complications, biliary function disorders, respiratory disorders such as snoring or sleep apneas and cardiovascular/central nervous system disorders such as stroke. More specifically, the present invention relates to substituted 4-phenyl-tetrahydroisoquinolines defined by the formula I in which R1-R8 are defined herein.
摘要翻译：本发明涉及取代的4-苯基四氢异喹啉化合物和包含它们的药物组合物，它们是钠 - 氢交换器（NHE），特别是亚型3（NHE-3）的钠氢交换器的优异抑制剂。因此，这些化合物可用于治疗肾脏和呼吸系统的各种疾病，例如急性或慢性肾衰竭，肺并发症，胆汁功能障碍，呼吸系统疾病如打鼾或睡眠呼吸暂停和心血管/中枢神经系统疾病，例如行程。更具体地，本发明涉及由式I定义的取代的4-苯基 - 四氢异喹啉，其中R 1 -R 8在本文中定义。

2. 发明授权

US07763643B2 Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis 有权
标题翻译：取代的噻吩：组合物，制备方法和用于疾病治疗和诊断中的用途
公开(公告)号：US07763643B2
公开(公告)日：2010-07-27
申请号：US12363030
申请日：2009-01-30
申请人： Hans-Jochen Lang , Uwe Heinelt , Armin Hofmeister , Klaus Wirth , Michael Gekle , Markus Bleich
发明人： Hans-Jochen Lang , Uwe Heinelt , Armin Hofmeister , Klaus Wirth , Michael Gekle , Markus Bleich
IPC分类号： A61K31/4178
CPC分类号： C07D409/12 , A61K31/4184 , A61K31/454
摘要： The present invention comprises compounds and compositions comprising substituted thiophene derivatives with the following backbone structure: The compounds of this type are of useful in the treatment of various disorders, such as, respiratory disorders and snoring, acute and chronic disorders, disorders induced by ischemic and/or reperfusion events and by proliferative or fibrotic events, disorders of the central nervous system and lipid metabolism, diabetes, blood coagulation and infection by parasites.
摘要翻译：本发明包括具有以下骨架结构的取代噻吩衍生物的化合物和组合物：这种类型的化合物可用于治疗各种疾病，例如呼吸系统疾病和打鼾，急性和慢性疾病，由缺血性和 /或再灌注事件以及增殖或纤维化事件，中枢神经系统疾病和脂质代谢，糖尿病，凝血和寄生虫感染。

3. 发明授权

US07556931B2 Furosemide modulators of HM74 失效
标题翻译： HM74的呋塞米调节剂
公开(公告)号：US07556931B2
公开(公告)日：2009-07-07
申请号：US11745131
申请日：2007-05-07
申请人： Ann Minnich , Theresa Kuntzweiler , Haifeng Eishingdrelo , Michael Angelastro , Hans-Jochen Lang
发明人： Ann Minnich , Theresa Kuntzweiler , Haifeng Eishingdrelo , Michael Angelastro , Hans-Jochen Lang
IPC分类号： G01N33/566 , A61K31/33 , A61K31/41 , A61K31/335
CPC分类号： C07D333/20 , C07D207/335 , C07D307/52
摘要： Host cells expressing HM74 were used to obtain furosemide-like molecules with agonist activity having the following structure formula:
摘要翻译：使用表达HM74的宿主细胞获得具有下列结构式的激动剂活性的呋塞米样分子：

4. 发明申请

US20090143473A1 USE OF INHIBITORS OF THE CELLULAR NA+/H+ EXCHANGER (NHE) FOR PREPARING A MEDICAMENT FOR NORMALIZING SERUM LIPIDS 审中-公开
标题翻译：细胞NA + / H +交换子（NHE）的抑制剂用于制备用于正常化血清脂质的药物
公开(公告)号：US20090143473A1
公开(公告)日：2009-06-04
申请号：US12364703
申请日：2009-02-03
申请人： Hans Jochen LANG , Hans-Willi JANSEN , Jan-Robert SCHWARK , Heinz-Werner KLEEMANN , Oliver JUNG , Hans-Ludwig SCHAFER , Wolfgang LINZ , Werner KRAMER , Bernward SCHOLKENS , Eugen FALK
发明人： Hans Jochen LANG , Hans-Willi JANSEN , Jan-Robert SCHWARK , Heinz-Werner KLEEMANN , Oliver JUNG , Hans-Ludwig SCHAFER , Wolfgang LINZ , Werner KRAMER , Bernward SCHOLKENS , Eugen FALK
IPC分类号： A61K31/165 , A61P7/00
CPC分类号： A61K31/00 , A61K31/155 , A61K31/166 , A61K31/22 , A61K31/365 , A61K2300/00
摘要： Use of inhibitors of the cellular Na+/H+ exchanger (NHE) for the production of a medicament for the normalization of serum lipids.The active compounds identified as inhibitors of the cellular Na+/H+ exchanger (NHE) are used for the production of a medicament for the normalization of serum lipids.They are used for the production of a medicament for lowering the blood lipid level and illnesses caused thereby, as well as the endothelial dysfunction syndrome and illness caused thereby.
摘要翻译：使用细胞Na + / H +交换剂（NHE）的抑制剂来制备用于血清脂质标准化的药物。鉴定为细胞Na + / H +交换体（NHE）的抑制剂的活性化合物用于制备用于血清脂质标准化的药物。它们用于制备用于降低由此引起的血脂水平和疾病以及由此引起的内皮功能障碍综合征和疾病的药物。

5. 发明申请

US20080275098A1 NOVEL SUBSTITUTED 2-AMINOIMIDAZOLES, PROCESS FOR THEIR PREPARATION, THEIR USE AS MEDICAMENT OR DIAGNOSTIC AID 审中-公开
标题翻译：新型取代的2-氨基嘧啶，其制备方法，用作药物或诊断辅助剂
公开(公告)号：US20080275098A1
公开(公告)日：2008-11-06
申请号：US12172380
申请日：2008-07-14
申请人： Uwe HEINELT , Hans-Jochen LANG , Armin HOFMEISTER , Klaus WIRTH , Hans-Willi JANSEN
发明人： Uwe HEINELT , Hans-Jochen LANG , Armin HOFMEISTER , Klaus WIRTH , Hans-Willi JANSEN
IPC分类号： C07D233/50 , A61K31/4168 , C07D235/30 , C07D317/72 , A61P9/10 , A61P3/00 , A61P3/10 , C07D317/10 , A61K31/4184
CPC分类号： C07D233/50
摘要： The present invention comprises novel substituted 2-aminoimidazoles of formula I, processes for their preparation, pharmaceutical compositions thereof, and methods for their use in the treatment of disorders of the central nervous system, cardiovascular disorders, stroke and pulmonary disorders, urinary disorders such as acute or chronic renal failure, disorders of biliary function, respiratory disorders such as snoring or sleep apnea. wherein the substitutents R1-R8 are further defined herein.
摘要翻译：本发明包括式I的新型取代的2-氨基咪唑，其制备方法，其药物组合物及其用于治疗中枢神经系统疾病，心血管疾病，中风和肺部疾病的方法，尿障碍如急性或慢性肾衰竭，胆汁功能障碍，呼吸系统疾病如打鼾或睡眠呼吸暂停。其中取代基R1-R8在本文中进一步定义。

6. 发明申请

US20080234317A1 METHODS FOR THE IMPROVEMENT OF MEMORY AND NEUROLOGICAL FUNCTION COMPRISING THE ADMINISTRATION OF COMPOSITIONS THAT ACT AS INHIBITORS OF THE SODIUM PROTON (NA+ /H+ ) EXCHANGER, SUBTYPE 5 (NHE-5) 审中-公开
标题翻译：改进存储器和神经功能的方法，包括作为钠原子（NA + / H +）交换剂，第5类（NHE-5）交换剂的抑制剂的组合物的管理，
公开(公告)号：US20080234317A1
公开(公告)日：2008-09-25
申请号：US12046920
申请日：2008-03-12
申请人： Heinz-Werner KLEEMANN , Hans-Jochen LANG , Uwe HEINELT , Armin HOFMEISTER , Holger GAUL , Ulrich Hendrich SCHROEDER , Klaus REYMANN
发明人： Heinz-Werner KLEEMANN , Hans-Jochen LANG , Uwe HEINELT , Armin HOFMEISTER , Holger GAUL , Ulrich Hendrich SCHROEDER , Klaus REYMANN
IPC分类号： A61K31/47 , A61P25/00
CPC分类号： A61K31/47
摘要： The present invention comprises the use of pharmaceutical compositions that are effective in the inhibition of the Na+/H+ exchanger, subtype 5 (NHE-5) as inhibitors of cellular NHE-5 enhance long term potentiation (LTP) and are therefore effective in the treatment of memory impairments, dementing disorders, and for improving memory. Particularly suitable for the treatment of neurodegenerative disorders, memory impairments and dementing disorders, and for improving memory, are the following NHE-5 inhibitors of the formula I Wherein the R1-R8 substituents are further defined herein:
摘要翻译：本发明包括使用有效抑制作为细胞NHE抑制剂的第5型（NHE-5）型的Na + / H + -5增强长期增强（LTP），因此有效治疗记忆障碍，痴呆症和改善记忆。特别适用于治疗神经变性疾病，记忆障碍和痴呆病症以及改善记忆力，是下列式I的NHE-5抑制剂，其中R1-R8取代基在本文中进一步定义：

7. 发明申请

US20080146797A1 PROCESS FOR SYNTHESIZING HETEROCYCLIC COMPOUNDS 有权
标题翻译：合成杂环化合物的方法
公开(公告)号：US20080146797A1
公开(公告)日：2008-06-19
申请号：US12026746
申请日：2008-02-06
申请人： Uwe HEINELT , Hans-Jochen LANG
发明人： Uwe HEINELT , Hans-Jochen LANG
IPC分类号： C07D265/06 , C07D233/06 , C07D277/08 , C07D235/04 , C07D263/52 , C07D235/02 , C07D409/02
CPC分类号： C07D413/12 , C07D233/50 , C07D235/30 , C07D263/28 , C07D263/58 , C07D265/08 , C07D265/12 , C07D265/18 , C07D277/18 , C07D409/12 , C07D495/04
摘要： The invention provides the process illustrated in scheme 1 for synthesizing heterocyclic compounds of formula I. In the process, an isothiocyanate of formula II is initially reacted with a primary amine or formula III to give a thiourea of formula IV. Subsequently, the thiourea of formula IV is converted to the corresponding heterocycle of formula I using a base and a sulfonyl chloride.
摘要翻译：本发明提供了用于合成式I的杂环化合物的方案1中所示的方法。在该方法中，式II的异硫氰酸酯最初与伯胺或式III反应，得到式IV的硫脲。随后，使用碱和磺酰氯将式IV的硫脲转化成相应的式I的杂环。

8. 发明申请

US20080058328A1 SUBSTITUTED 4-PHENYLTETRAHYDROISOQUINOLINES, PHARMACEUITCAL COMPOSITIONS COMPRISING THEM AND THERAPEUTIC METHODS FOR THEIR USE 有权
标题翻译：取代的4-苯基恶唑啉酮，包含它们的药物组合物及其使用的治疗方法
公开(公告)号：US20080058328A1
公开(公告)日：2008-03-06
申请号：US11776041
申请日：2007-07-11
申请人： Uwe HEINELT , Hans-Jochen LANG , Klaus WIRTH , Thomas LICHER , Armin HOFMEISTER
发明人： Uwe HEINELT , Hans-Jochen LANG , Klaus WIRTH , Thomas LICHER , Armin HOFMEISTER
IPC分类号： C07D217/12 , A61K31/47 , A61K31/5377 , A61P13/00 , C07D413/10 , A61P25/00 , A61P33/00 , A61P9/00
CPC分类号： C07D401/10 , C07D217/18
摘要： The invention relates to substituted 4-phenyltetrahydroisoquinolines of formula I wherein R1-R8, N, W, X and Z are defined herein. These compounds and pharmaceutical compositions comprising them are useful in the treatment of respiratory disorders, sleep apnea, kidney disorders, high blood pressure, hypertension, disorders of the central nervous system and the like.
摘要翻译：本发明涉及式I的取代的4-苯基四氢异喹啉，其中R1-R8，N，W，X和Z如本文所定义。这些化合物和包含它们的药物组合物可用于治疗呼吸障碍，睡眠呼吸暂停，肾脏疾病，高血压，高血压，中枢神经系统疾病等。

9. 发明授权

US07317033B2 Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis 有权
标题翻译：取代的噻吩：组合物，制备方法和用于疾病治疗和诊断中的用途
公开(公告)号：US07317033B2
公开(公告)日：2008-01-08
申请号：US11385331
申请日：2006-03-21
申请人： Hans-Jochen Lang , Uwe Heinelt , Armin Hofmeister , Klaus Wirth , Michael Gekle , Markus Bleich
发明人： Hans-Jochen Lang , Uwe Heinelt , Armin Hofmeister , Klaus Wirth , Michael Gekle , Markus Bleich
IPC分类号： A61K31/4178
CPC分类号： C07D409/12 , A61K31/4184 , A61K31/454
摘要： Substituted thiophenes, processes for their preparation, their use as medicament or diagnostic agent. The substituted thiophene derivatives have the following backbone structure: Medicaments comprising compounds of this type are of use for preventing or treating various disorders, such as, respiratory disorders and snoring, acute and chronic disorders, disorders induced by ischemic and/or reperfusion events and by proliferative or fibrotic events, disorders of the central nervous system and lipid metabolism, diabetes, blood coagulation and infection by parasites.
摘要翻译：取代的噻吩，其制备方法，其用作药物或诊断剂。取代的噻吩衍生物具有以下骨架结构：包含这种类型的化合物的药物可用于预防或治疗各种疾病，例如呼吸障碍和打鼾，急性和慢性疾病，由缺血和/或再灌注事件诱导的疾病，以及由增生或纤维化事件，中枢神经系统疾病和脂质代谢，糖尿病，凝血和寄生虫感染。

10. 发明申请

US20070265278A1 2-PHENYL-INDOLES AS PROSTAGLANDIN D2 RECEPTOR ANTAGONISTS 审中-公开
标题翻译： 2-PHENYL-INDOLES作为PROSTAGLANDIN D2受体拮抗剂
公开(公告)号：US20070265278A1
公开(公告)日：2007-11-15
申请号：US11782890
申请日：2007-07-25
申请人： Keith HARRIS , Hans-Jochen Lang , Rose Mathew , Stephen Shimshock , Thaddeus Nieduzak , Sharon Jackson , Zhaoxia Yang , Kenneth Bordeau
发明人： Keith HARRIS , Hans-Jochen Lang , Rose Mathew , Stephen Shimshock , Thaddeus Nieduzak , Sharon Jackson , Zhaoxia Yang , Kenneth Bordeau
IPC分类号： A61K31/404 , A61K31/4245 , A61K31/435 , A61K31/4453 , A61K31/47 , A61K31/495 , A61P1/04 , A61P37/08 , A61P9/00 , C07D209/04 , C07D271/113 , C07D401/12
CPC分类号： C07D209/12 , C07D209/18 , C07D209/22 , C07D209/24 , C07D405/12 , C07D413/06
摘要： The present invention is directed to a compound of Formula (XVI): (please replace Formula (I) with Formula (XVI) as shown below) wherein R, R2, R3, R4, R5, R6, R7 and n are as defined herein, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, a pharmaceutically acceptable prodrug thereof, or a pharmaceutically acceptable salt, hydrate or solvate of the prodrug, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds according to Formula (XVI) in admixture with a pharmaceutically acceptable carrier, a method of treating a patient suffering from a PGD2-mediated disorder including, but not limited to, allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, bronchitis, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which are generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like by administering to said patient a pharmaceutically effective amount of a compound according to Formula (XVI).
摘要翻译：本发明涉及式（ⅩⅥ）化合物：（如下所示，用式（ⅩⅥ）表示的式（I）表示）其中R，R 2，R 3， R 4，R 4，R 5，R 6，R 7和n如本文所定义，或其药学上可接受的盐，水合物或溶剂化物，其药学上可接受的前药，或药学上可接受的盐，水合物或溶剂化物，药物组合物，其包含药学上有效量的根据式（XVI）的一种或多种化合物与药学上可接受的载体混合，治疗患有PGD2介导的病症的患者的方法，包括但不限于过敏性疾病（例如过敏性鼻炎，过敏性结膜炎，特应性皮炎，支气管哮喘和食物过敏），全身肥大细胞增多症，伴有系统性肥大细胞活化，过敏性休克，支气管收缩，支气管炎，荨麻疹，湿疹，伴有瘙痒的疾病（如特应性皮炎和荨麻疹），伴随瘙痒的行为（如刮伤和殴打）而产生的疾病（如白内障，视网膜脱离，炎症，感染和睡眠障碍），炎症，慢性阻塞性肺疾病，缺血再灌注损伤，脑血管意外，慢性类风湿性关节炎，胸膜炎，溃疡性结肠炎等，通过向所述患者施用药学有效量的根据式（XVI）的化合物。

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