公开(公告)号：US07790742B2

公开(公告)日：2010-09-07

申请号：US11680668

申请日：2007-03-01

申请人： Hans-Jochen Lang ,  Uwe Heinelt ,  Klaus Wirth ,  Thomas Licher ,  Armin Hofmeister

发明人： Hans-Jochen Lang ,  Uwe Heinelt ,  Klaus Wirth ,  Thomas Licher ,  Armin Hofmeister

IPC分类号： C07D217/00 ,  A61K31/47

CPC分类号： C07D405/12 ,  C07D217/14 ,  C07D401/12

摘要： The present invention relates to substituted 4-phenyltetrahydroisoquinoline compounds of the structure of formula I and pharmaceutical compositions comprising them wherein the R groups are herein defined. These are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular of the sodium-hydrogen exchanger of subtype 3 (NHE3). 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, derivatives thereof and compositions containing them formulated in combination with other compounds which also regulate the intracellular pH environment such as inhibitors of carbonic anhydrase and inhibitors of the transport systems that carry bicarbonate ions, such as of the sodium-bicarbonate co-transporter (NBC) or the sodium-dependent chloride-bicarbonate exchanger.

摘要翻译： 本发明涉及式I结构的取代的4-苯基四氢异喹啉化合物和包含它们的药物组合物，其中本文定义了R基团。 这些是钠 - 氢交换器（NHE），特别是亚型3（NHE3）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，本发明涉及取代的4-苯基 - 四氢异喹啉，其衍生物和含有它们的组合物，其与调节细胞内pH环境的其它化合物配制，例如碳酸酐酶抑制剂和携带碳酸氢根离子的运输系统的抑制剂 ，例如碳酸氢钠共转运体（NBC）或钠依赖性氯化碳 - 碳酸氢盐交换剂。

公开(公告)号：US07868003B2

公开(公告)日：2011-01-11

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

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。

公开(公告)号：US08067614B2

公开(公告)日：2011-11-29

申请号：US12722634

申请日：2010-03-12

申请人： Uwe Heinelt ,  Hans-Jochen Lang ,  Armin Hofmeister ,  Klaus Wirth ,  Martin Hug

发明人： Uwe Heinelt ,  Hans-Jochen Lang ,  Armin Hofmeister ,  Klaus Wirth ,  Martin Hug

IPC分类号： A61K31/4184 ,  C07D235/30

CPC分类号： C07D235/30

摘要： This invention is directed to the compound of formula (I), compositions containing said compounds to inhibit the sodium-proton exchanger of subtype 3 (NHE3) which are useful in the prevention or treatment of various disorders in a patient suffering from a disease state, such as, renal disorders including acute or chronic renal failure, disorders of biliary function and for respiratory disorders such as snoring or sleep apnea or for stroke.

摘要翻译： 本发明涉及式（I）化合物，含有抑制亚型3（NHE3）的钠 - 质子交换剂的所述化合物的组合物，其可用于预防或治疗患有疾病状态的患者中的各种疾病， 例如包括急性或慢性肾衰竭，胆汁功能障碍和呼吸系统疾病如打鼾或睡眠呼吸暂停或中风的肾脏疾病。

公开(公告)号：US07442717B2

公开(公告)日：2008-10-28

申请号：US10771185

申请日：2004-02-03

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： A61K31/4168 ,  C07D233/88

CPC分类号： C07D233/50

摘要： Novel substituted 2-aminoimidazoles of formula I, process for their preparation, their use as medicament or diagnostic aid, and medicament containing them. The compounds of this type are useful in the prevention or treatment of various disorders and can be employed inter alia for renal disorders such as acute or chronic renal failure, for disorders of biliary function, for respiratory disorders such as snoring or sleep apneas or for stroke

摘要翻译： 式I的新型取代的2-氨基咪唑，其制备方法，它们作为药物或诊断助剂的用途以及含有它们的药物。 这种类型的化合物可用于预防或治疗各种疾病，并且可以特别用于肾脏疾病如急性或慢性肾衰竭，胆汁功能障碍，呼吸障碍如打鼾或睡眠呼吸暂停或中风

公开(公告)号：US06686384B2

公开(公告)日：2004-02-03

申请号：US10000028

申请日：2001-12-04

申请人： Armin Hofmeister ,  Uwe Heinelt ,  Hans-Jochen Lang ,  Markus Bleich ,  Klaus Wirth ,  Michael Gekle

发明人： Armin Hofmeister ,  Uwe Heinelt ,  Hans-Jochen Lang ,  Markus Bleich ,  Klaus Wirth ,  Michael Gekle

IPC分类号： A61K314184

CPC分类号： C07D235/30

摘要： The invention relates to the use of compounds of formula I for the production of a medicament for the treatment of illnesses which can be influenced by inhibition of the Na+/H+ exchanger, and to a medicament comprising them: in which R1 to R9 have the meanings shown in the claims.

摘要翻译： 本发明涉及式I化合物用于制备可受Na + / H +交换剂的抑制影响的疾病的药物的用途，以及包含它们的药物的用途：其中R 1至R 9具有以下含义： 如权利要求中所示。

公开(公告)号：US20050054705A1

公开(公告)日：2005-03-10

申请号：US10770654

申请日：2004-02-03

申请人： Uwe Heinelt ,  Hans-Jochen Lang ,  Armin Hofmeister ,  Klaus Wirth ,  Martin Hug

发明人： Uwe Heinelt ,  Hans-Jochen Lang ,  Armin Hofmeister ,  Klaus Wirth ,  Martin Hug

IPC分类号： C07D235/30 ,  A61K31/4184

CPC分类号： C07D235/30

摘要： This invention is directed to the compound of formula (I), compositions containing said compounds to inhibit the sodium-proton exchanger of subtype 3 (NHE3) which are useful in the prevention or treatment of various disorders in a patient suffering from a disease state, such as, renal disorders including acute or chronic renal failure, disorders of biliary function and for respiratory disorders such as snoring or sleep apnea or for stroke.

摘要翻译： 本发明涉及式（I）化合物，含有抑制亚型3（NHE3）的钠 - 质子交换剂的所述化合物的组合物，其可用于预防或治疗患有疾病状态的患者中的各种疾病， 例如包括急性或慢性肾衰竭，胆汁功能障碍和呼吸系统疾病如打鼾或睡眠呼吸暂停或中风的肾脏疾病。

公开(公告)号：US20050009864A1

公开(公告)日：2005-01-13

申请号：US10866843

申请日：2004-06-14

申请人： Armin Hofmeister ,  Uwe Heinelt ,  Hans-Jochen Lang ,  Markus Bleich ,  Klaus Wirth ,  Michael Gekle

发明人： Armin Hofmeister ,  Uwe Heinelt ,  Hans-Jochen Lang ,  Markus Bleich ,  Klaus Wirth ,  Michael Gekle

IPC分类号： C07D217/18 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  A61K31/47 ,  C07D217/02

CPC分类号： C07D401/12 ,  C07D217/18 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

摘要： The invention relates to compounds of the formula I in which R1 to R9 are as defined herein. In one embodiment, these compounds may be used as antihypertensives, for reducing or preventing ischemia-induced damage, as medicaments for surgical intervention for the treatment of ischemias of the nervous system, of stroke and of cerebral edema, of shock, of impaired respiratory drive, for the treatment of snoring, as laxative, as agent against ectoparasites, to prevent the formation of gallstones, as antiatherosclerotics, agents against late complications of diabetes, cancers, fibrotic disorders, endothelial dysfunction, organ hypertrophies and hyperplasias. In one embodiment, the compounds may be inhibitors of the cellular sodium-proton antiporter and influence serum lipoproteins and thus be used for the prophylaxis and for the regression of atherosclerotic lesions.

公开(公告)号：US20060160873A1

公开(公告)日：2006-07-20

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.

公开(公告)号：US20050009863A1

公开(公告)日：2005-01-13

申请号：US10807781

申请日：2004-03-24

申请人： Armin Hofmeister ,  Uwe Heinelt ,  Hans-Jochen Lang ,  Wendelin Frick ,  Markus Bleich ,  Klaus Wirth

发明人： Armin Hofmeister ,  Uwe Heinelt ,  Hans-Jochen Lang ,  Wendelin Frick ,  Markus Bleich ,  Klaus Wirth

IPC分类号： A61K31/47 ,  C07D217/12

CPC分类号： C07D217/22

摘要： Substituted 4-phenyltetrahydroisoquinolines of formula I, process for their preparation, their use as a medicament and medicaments containing them. The compounds of formula I can be used, among other uses, in the event of renal disorders such as acute or chronic renal failure, in the event of disorders of biliary function, in the event of respiratory disorders such as snoring or sleep apneas or in the event of stroke.

摘要翻译： 取代的式I的4-苯基四氢异喹啉，其制备方法，它们作为药物的用途和含有它们的药物。 在发生诸如急性或慢性肾功能衰竭的肾脏疾病，在胆汁功能紊乱的情况下，在呼吸障碍如打鼾或睡眠呼吸暂停的情况下，式I化合物可以用于其它用途，或在 中风事件。

公开(公告)号：US20050004198A1

公开(公告)日：2005-01-06

申请号：US10892994

申请日：2004-07-16

申请人： Uwe Heinelt ,  Hans-Jochen Lang ,  Armin Hofmeister ,  Klaus Wirth

发明人： Uwe Heinelt ,  Hans-Jochen Lang ,  Armin Hofmeister ,  Klaus Wirth

IPC分类号： C07D233/50 ,  C07D233/66 ,  C07D233/91 ,  C07D235/02 ,  C07D235/30

CPC分类号： C07D235/02 ,  C07D233/50 ,  C07D235/30

摘要： The invention relates to novel compounds of the type of the imidazolidines of the formula I in which R1 to R7 are as defined in the claims. They are used for preparing a medicament for the treatment or prophylaxis of the central nervous system, of lipid metabolism, of infection by ectoparasites, of disorders of gall function and for improving the respiratory drive and are therefore used for treating respiratory distress. Additionally, the compounds increase the muscle tone of the upper respiratory tract, thus suppressing snoring.

摘要翻译： 本发明涉及式I的咪唑烷类型的新化合物，其中R 1至R 7如权利要求中所定义。 它们用于制备用于治疗或预防中枢神经系统，脂质代谢，外寄生虫感染，胆汁功能障碍和改善呼吸驱动的药物，因此用于治疗呼吸窘迫。 此外，化合物增加上呼吸道的肌肉紧张度，从而抑制打鼾。