公开(公告)号：US07612104B2

公开(公告)日：2009-11-03

申请号：US12062759

申请日：2008-04-04

申请人： Karl Schoenafinger ,  Stefanie Keil ,  Matthias Urmann ,  Hans Matter ,  Maike Glien ,  Wolfgang Wendler

发明人： Karl Schoenafinger ,  Stefanie Keil ,  Matthias Urmann ,  Hans Matter ,  Maike Glien ,  Wolfgang Wendler

IPC分类号： A61K31/433 ,  C07D285/135

CPC分类号： C07D417/12 ,  C07D285/135

摘要： The present invention comprises bicyclic aryl-sulfonic acid [1,3,4]-thiadiazol-2-yl-amides, their functional derivatives thereof as well as their physiologically acceptable salts and pharmaceutical compositions thereof that exhibit peroxisome proliferator activated receptor (PPAR) PPARdelta and PPARgamma agonist activity. The structure of the compounds of the invention are defined by Formula I below, wherein the various substituents are defined herein, including their physiologically acceptable salts. Processes for the compounds preparation are also disclosed. The compounds are suitable for the treatment of fatty acid metabolism and glucose utilization disorders, disorders relating to insulin resistance are involved as well as demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

摘要翻译： 本发明包括双环芳基磺酸[1,3,4] - 噻二唑-2-基 - 酰胺，它们的功能衍生物及其生理上可接受的盐和药物组合物，其表现出过氧化物酶体增殖物激活受体（PPAR）PPARδ 和PPARγ激动剂活性。 本发明化合物的结构由下式I定义，其中各种取代基在本文中定义，包括其生理上可接受的盐。 还公开了化合物制备的方法。 该化合物适用于治疗脂肪酸代谢和葡萄糖利用障碍，涉及胰岛素抵抗的疾病以及中枢和周围神经系统的脱髓鞘和其他神经变性疾病。

公开(公告)号：US07576109B2

公开(公告)日：2009-08-18

申请号：US11535227

申请日：2006-09-26

申请人： Daniel G. McGarry ,  Karen Chandross ,  Jean Merrill ,  Jochen Goerlitzer ,  Stefanie Keil ,  Wolfgang Wendler ,  Patrick Bernardelli

发明人： Daniel G. McGarry ,  Karen Chandross ,  Jean Merrill ,  Jochen Goerlitzer ,  Stefanie Keil ,  Wolfgang Wendler ,  Patrick Bernardelli

IPC分类号： A61K31/4245 ,  C07D271/10 ,  C07D413/10

CPC分类号： C07D417/12

摘要： The present invention is directed to 1,3,4-oxadiazolones, compounds of formula I and their pharmaceutically acceptable salts stereoisomers, tautomers, or solvates thereof. Novel compounds include those of formula I, in which radicals are as defined herein. The compounds of this invention are modulators of PPARdelta and therefore useful as pharmaceutical agents, especially for the treatment of demyelinating diseases and disorders of fatty acid metabolism and glucose utilization.

摘要翻译： 本发明涉及1,3,4-恶二唑酮，式I化合物及其药学上可接受的盐立体异构体，互变异构体或溶剂合物。 新型化合物包括式I化合物，其中基团如本文所定义。 本发明的化合物是PPARdta的调节剂，因此可用作药剂，特别是用于治疗脱髓鞘疾病和脂肪酸代谢和葡萄糖利用的障碍。

公开(公告)号：US20090054494A1

公开(公告)日：2009-02-26

申请号：US12062764

申请日：2008-04-04

申请人： Stefanie KEIL ,  Hans MATTER ,  Karl SCHOENAFINGER ,  Mathias URMANN ,  Maike GLIEN ,  Wolfgang WENDLER ,  Hans-Ludwig SCHAEFER ,  Eugen FALK

发明人： Stefanie KEIL ,  Hans MATTER ,  Karl SCHOENAFINGER ,  Mathias URMANN ,  Maike GLIEN ,  Wolfgang WENDLER ,  Hans-Ludwig SCHAEFER ,  Eugen FALK

IPC分类号： A61K31/433 ,  C07D285/135 ,  A61K31/4439 ,  A61P3/00 ,  C07D417/12

CPC分类号： C07D417/12 ,  C07D285/135

摘要： The present invention comprises N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides, their physiologically acceptable salts and functional derivatives that exhibit peroxisome proliferator activated receptor (PPAR) PPARdelta and PPARgamma agonist activity. The structure of the compounds of the invention are defined by Formula I below, And the isomers thereof wherein the various substituents are defined herein, including their physiologically acceptable salts. Processes for the compounds preparation are also disclosed. The compounds are suitable for the treatment of fatty acid metabolism and glucose utilization disorders, disorders relating to insulin resistance are involved as well as demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

摘要翻译： 本发明包括显示过氧化物酶体增殖物激活受体（PPAR）PPARδ和PPARγ激动剂活性的N- [1,3,4] - 噻二唑-2-基 - 苯磺酰胺，其生理上可接受的盐和功能性衍生物。 本发明化合物的结构由下式I定义，其各种取代基在本文中定义的异构体，包括其生理上可接受的盐。 还公开了化合物制备的方法。 该化合物适用于治疗脂肪酸代谢和葡萄糖利用障碍，涉及胰岛素抵抗的疾病以及中枢和周围神经系统的脱髓鞘和其他神经变性疾病。

公开(公告)号：US20080280959A1

公开(公告)日：2008-11-13

申请号：US12062753

申请日：2008-04-04

申请人： Karl SCHOENAFINGER ,  Stefanie KEIL ,  Matthias URMANN ,  Hans MATTER ,  Maike GLIEN ,  Wolfgang WENDLER

发明人： Karl SCHOENAFINGER ,  Stefanie KEIL ,  Matthias URMANN ,  Hans MATTER ,  Maike GLIEN ,  Wolfgang WENDLER

IPC分类号： A61K31/433 ,  C07D285/135 ,  A61P3/00

CPC分类号： C07D417/12 ,  C07D285/135

摘要： The present invention comprises cyclic N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides, their functional derivatives as well as their physiologically acceptable salts and pharmaceutical compositions thereof that exhibit peroxisome proliferator activated receptor (PPAR) PPARdelta and PPARgamma agonist activity. The structure of the compounds of the invention are defined by Formula I below, wherein the various R1-R9 substituents are defined herein. Processes for the compounds preparation are also disclosed. The compounds are suitable for the treatment of fatty acid metabolism and glucose utilization disorders, disorders relating to insulin resistance are involved as well as demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

摘要翻译： 本发明包括环状N- [1,3,4] - 噻二唑-2-基 - 苯磺酰胺，它们的功能衍生物及其生理上可接受的盐和药物组合物，其表现出过氧化物酶体增殖物激活受体（PPAR）PPARδ和PPARγ 激动剂活性。 本发明化合物的结构由下式I定义，其中各种R1-R9取代基在本文中定义。 还公开了化合物制备的方法。 该化合物适用于治疗脂肪酸代谢和葡萄糖利用障碍，涉及胰岛素抵抗的疾病以及中枢和周围神经系统的脱髓鞘和其他神经变性疾病。

公开(公告)号：US20080262036A1

公开(公告)日：2008-10-23

申请号：US12055764

申请日：2008-03-26

申请人： Stefanie Keil ,  Patrick Bernardelli ,  Matthias Urmann ,  Hans Matter ,  Wolfgang Wendler ,  Maike Glien ,  Karen Chandross ,  Lan Lee

发明人： Stefanie Keil ,  Patrick Bernardelli ,  Matthias Urmann ,  Hans Matter ,  Wolfgang Wendler ,  Maike Glien ,  Karen Chandross ,  Lan Lee

IPC分类号： A61K31/4709 ,  C07D417/12 ,  A61K31/427 ,  A61P3/10 ,  A61P3/00 ,  A61K31/454 ,  C07D417/14

CPC分类号： C07D417/14 ,  C07D277/24 ,  C07D417/12

摘要： The present invention comprises phenyl-[1,2,4]-oxadiazol-5-one derivatives of the general formula I: wherein the R1-R10 and B, U, V, W, X, Y and Z substituents are defined herein. The claimed invention also comprises the compounds isomers and their physiologically acceptable salts as well as processes for their preparation. The compounds are suitable for the treatment and/or prevention of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistance is involved and demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

摘要翻译： 本发明包括通式I的苯基 - [1,2,4] - 恶二唑-5-酮衍生物：其中R1-R10和B，U，V，W，X，Y和Z取代基在本文中定义。 所要求保护的发明还包括化合物异构体及其生理学上可接受的盐以及其制备方法。 该化合物适用于治疗和/或预防脂肪酸代谢紊乱和葡萄糖利用障碍以及其中涉及胰岛素抵抗和中枢神经和周围神经系统的脱髓鞘和其它神经变性疾病的疾病。

公开(公告)号：US20080261979A1

公开(公告)日：2008-10-23

申请号：US12055780

申请日：2008-03-26

申请人： Stefanie Keil ,  Matthias Urmann ,  Patrick Bernardelli ,  Maike Glien ,  Wolfgang Wendler ,  Karen Chandross ,  Lan Lee

发明人： Stefanie Keil ,  Matthias Urmann ,  Patrick Bernardelli ,  Maike Glien ,  Wolfgang Wendler ,  Karen Chandross ,  Lan Lee

IPC分类号： A61K31/5377 ,  C07D413/12 ,  A61K31/4245 ,  A61P3/00 ,  C07D413/14

CPC分类号： C07D417/12 ,  C07D417/14

摘要： The inventive compounds of the present invention are comprised of phenyl and pyridinyl-1,2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives that are shown to provide peroxisome proliferator activator receptor (PPARdelta) agonist activity. The compounds of the present invention are comprised of the formula: wherein the substituents R1-R5 and R7-R10 are defined herein. The compounds are therapeutically effective in the regulation and modulation of lipid and carbohydrate metabolism in mammals and are thus suitable for the treatment of diseases such as type-2 diabetes, atherosclerosis, cardiovascular disorders and the like.

摘要翻译： 本发明的本发明化合物包括苯基和吡啶基-1,2,4-恶二唑酮衍生物及其生理上可接受的盐和功能性衍生物，其被证明能提供过氧化物酶体增殖物激活剂受体（PPARδ）激动剂活性。 本发明的化合物由下式构成：其中取代基R 1 -R 5和R 7 -R 10在本文中定义。 该化合物在哺乳动物中调节和调节脂质和碳水化合物代谢方面具有治疗上的有效性，因此适用于治疗诸如2型糖尿病，动脉粥样硬化，心血管疾病等疾病。

公开(公告)号：US20080171776A1

公开(公告)日：2008-07-17

申请号：US11949833

申请日：2007-12-04

申请人： Christian STAPPER ,  Heiner GLOMBIK ,  Eugen FALK ,  Stefanie KEIL ,  Hans-Ludwig SCHAEFER ,  Wolfgang WENDLER ,  Stephanie HACHTEL

发明人： Christian STAPPER ,  Heiner GLOMBIK ,  Eugen FALK ,  Stefanie KEIL ,  Hans-Ludwig SCHAEFER ,  Wolfgang WENDLER ,  Stephanie HACHTEL

IPC分类号： A61K31/421 ,  C07D263/32 ,  A61P3/00 ,  A61P3/10 ,  A61P3/08

CPC分类号： C07D263/32 ,  C07D413/04

摘要： The present invention comprises compounds and compositions for the treatment of metabolic disorders and more particularly, those insulin-related metabolic disorders of the blood such as hyperlipidemia, diabetes, insulin-resistance and the like comprising acetic acid derivatives with cyclohexylmethoxy substituents and their salts. Known as peroxisome proliferator-activated receptor (PPAR) agonists/antagonists, the invention relates to compounds of formula I wherein R1-R6 are further defined herein.

摘要翻译： 本发明包括用于治疗代谢紊乱的化合物和组合物，更具体地，涉及含有环己基甲氧基取代基的乙酸衍生物及其盐的血液中的这些与胰岛素有关的代谢性疾病如高脂血症，糖尿病，胰岛素抵抗等。 被称为过氧化物酶体增殖物激活受体（PPAR）激动剂/拮抗剂的本发明涉及式I化合物，其中R 1 -R 6在本文中进一步定义。

公开(公告)号：US20070099964A1

公开(公告)日：2007-05-03

申请号：US11535764

申请日：2006-09-27

申请人： Daniel McGarry ,  Jochen Goerlitzer ,  Stefanie Keil ,  Karen Chandros ,  Jean Merrill ,  Wolfgang Wendler

发明人： Daniel McGarry ,  Jochen Goerlitzer ,  Stefanie Keil ,  Karen Chandros ,  Jean Merrill ,  Wolfgang Wendler

IPC分类号： A61K31/4439 ,  A61K31/4245 ,  A61K31/427 ,  C07D413/14 ,  C07D417/14

CPC分类号： C07D417/12 ,  C07D277/24 ,  C07D277/30

摘要： The present invention is directed to 1,3,4-oxadiazalones, i.e., the compounds of formula I and their pharmaceutically acceptable salts, stereoisomers, tautomers, or solvates thereof. Novel compounds include those of formula I, in which radicals are as defined herein. The compounds of this invention are modulators of PPARdelta and therefore useful as pharmaceutical agents, especially for the treatment of demyelinating diseases and disorders of fatty acid metabolism and glucose utilization such as multiple scleroses.

摘要翻译： 本发明涉及1,3,4-恶二唑酮，即式I化合物及其药学上可接受的盐，立体异构体，互变异构体或溶剂合物。 新型化合物包括式I化合物，其中基团如本文所定义。 本发明的化合物是PPARdta的调节剂，因此可用作药剂，特别是用于治疗脱髓鞘疾病和脂肪酸代谢紊乱以及葡萄糖利用如多种硬化症。

公开(公告)号：US07173151B2

公开(公告)日：2007-02-06

申请号：US10789324

申请日：2004-02-27

申请人： Christian Stapper ,  Heiner Glombik ,  Eugen Falk ,  Dirk Gretzke ,  Jochen Goerlitzer ,  Stefanie Keil ,  Hans-Ludwig Schaefer ,  Wolfgang Wendler

发明人： Christian Stapper ,  Heiner Glombik ,  Eugen Falk ,  Dirk Gretzke ,  Jochen Goerlitzer ,  Stefanie Keil ,  Hans-Ludwig Schaefer ,  Wolfgang Wendler

IPC分类号： C07C229/00 ,  C07C61/28 ,  C07C61/16 ,  C07C62/00 ,  C07C62/30

CPC分类号： C07C275/28 ,  C07C275/10 ,  C07C275/24 ,  C07C275/26 ,  C07C2601/14

摘要： The invention relates to arylcycloalkyl-substituted derivatives and to their physiologically acceptable salts and physiologically functional derivatives.What is described are compounds of the formula I, in which the radicals are as defined, and their physiologically acceptable salts and processes for their preparation. The compounds are suitable for the treatment and/or prevention of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistence is involved.

摘要翻译： 本发明涉及芳基环烷基取代的衍生物及其生理上可接受的盐和生理功能衍生物。 描述的是式I化合物，其中基团如所定义，以及它们的生理上可接受的盐及其制备方法。 所述化合物适用于治疗和/或预防脂肪酸代谢紊乱和葡萄糖利用障碍以及涉及胰岛素抵抗的疾病。

公开(公告)号：US07148246B2

公开(公告)日：2006-12-12

申请号：US10789865

申请日：2004-02-27

申请人： Dirk Gretzke ,  Heiner Glombik ,  Eugen Falk ,  Jochen Goerlitzer ,  Stefanie Keil ,  Hans-Ludwig Schaefer ,  Christian Stapper ,  Wolfgang Wendler

发明人： Dirk Gretzke ,  Heiner Glombik ,  Eugen Falk ,  Jochen Goerlitzer ,  Stefanie Keil ,  Hans-Ludwig Schaefer ,  Christian Stapper ,  Wolfgang Wendler

IPC分类号： C07D277/04 ,  C07D209/54 ,  C07D257/04 ,  C07D413/00 ,  A61K31/42

CPC分类号： C07D417/12 ,  C07D263/32 ,  C07D413/12

摘要： Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals The invention relates to cycloalkyl derivatives having bioisosteric carboxylic acid groups and to their physiologically acceptable salts and physiologically functional derivatives. What is described are compounds of the formula I, in which the radicals are as defined, and their physiologically acceptable salts and processes for their preparations. The compounds are suitable for the treatment and/or prevention of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistence is involved.

摘要翻译： 具有生物硅烷酸羧酸基团的环烷基衍生物及其制备方法及其作为药物的用途本发明涉及具有生物硅烷酸羧酸基团的环烷基衍生物及其生理上可接受的盐和生理功能衍生物。 所描述的是式I化合物，其中自由基如所定义，以及它们的生理上可接受的盐及其制备方法。 所述化合物适用于治疗和/或预防脂肪酸代谢紊乱和葡萄糖利用障碍以及涉及胰岛素抵抗的疾病。