公开(公告)号：US07365088B2

公开(公告)日：2008-04-29

申请号：US10849088

申请日：2004-05-19

Applicant: Marc Nazare ,  Volkmar Wehner ,  Volker Laux ,  Matthias Urmann ,  Armin Bauer ,  Hans Matter

Inventor： Marc Nazare ,  Volkmar Wehner ,  Volker Laux ,  Matthias Urmann ,  Armin Bauer ,  Hans Matter

IPC: A16K31/42 ,  A16K31/4152 ,  C07D261/20 ,  C07D413/14

CPC classification number: C07D413/14 ,  C07D401/12 ,  C07D401/14

Abstract: The present invention relates to a compound of the formula I wherein J1, J2, R0, R1, R2, Q, V, G and M are as defined herein. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Abstract translation: 本发明涉及式I化合物，其中J 1，J 2，R 0，R 1，O 2， >，R 2，Q，V，G和M如本文所定义。 式I的化合物是有价值的药理活性化合物。 它们具有强烈的抗血栓形成作用，并且适用于例如治疗和预防心血管疾病如血栓栓塞性疾病或再狭窄。 它们是血液凝固酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆抑制剂，并且通常可用于存在因子Xa和/或因子VIIa的不期望活性或用于治愈 或预防因子Xa和/或因子VIIa的抑制。 本发明还涉及式I化合物的制备方法，其用途，特别是作为药物中的活性成分，以及包含它们的药物制剂。

公开(公告)号：US07317027B2

公开(公告)日：2008-01-08

申请号：US10849089

申请日：2004-05-19

Applicant: Marc Nazare ,  Volkmar Wehner ,  David William Will ,  Kurt Ritter ,  Matthias Urmann ,  Hans Matter

Inventor： Marc Nazare ,  Volkmar Wehner ,  David William Will ,  Kurt Ritter ,  Matthias Urmann ,  Hans Matter

IPC: A61K31/44 ,  C07D401/00

CPC classification number: C07D471/04

Abstract: The present invention relates to compounds of the formula I wherein R0, R1, R2, R3, Q, V, G and M are as defined herein. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Abstract translation: 本发明涉及式I化合物，其中R 0，R 1，R 2，R 3，R 3， ，Q，V，G和M如本文所定义。 式I的化合物是有价值的药理活性化合物。 它们具有强烈的抗血栓形成作用，并且适用于例如治疗和预防心血管疾病如血栓栓塞性疾病或再狭窄。 它们是血液凝固酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆抑制剂，并且通常可用于存在因子Xa和/或因子VIIa的不期望活性或用于治愈 或预防因子Xa和/或因子VIIa的抑制。 本发明还涉及式I化合物的制备方法，其用途，特别是作为药物中的活性成分，以及包含它们的药物制剂。

公开(公告)号：US07186724B2

公开(公告)日：2007-03-06

申请号：US10819037

申请日：2004-04-06

Applicant: James A Hendrix ,  Horst Hemmerle ,  Matthias Urmann ,  Gregory M Shutske ,  Jospeh T Strupczewski ,  Kenneth J Bordeau ,  John G Jurcak ,  Thaddeus Nieduzak ,  Sharon A Jackson ,  Paul Angell ,  James P Carey ,  George Lee ,  David Fink ,  Jean-Fancois Sabuco ,  Yulin Chiang ,  Nicola Collar

Inventor： James A Hendrix ,  Horst Hemmerle ,  Matthias Urmann ,  Gregory M Shutske ,  Jospeh T Strupczewski ,  Kenneth J Bordeau ,  John G Jurcak ,  Thaddeus Nieduzak ,  Sharon A Jackson ,  Paul Angell ,  James P Carey ,  George Lee ,  David Fink ,  Jean-Fancois Sabuco ,  Yulin Chiang ,  Nicola Collar

IPC: A61K31/496 ,  C07D409/04 ,  C07D409/14 ,  A61K31/4535 ,  A61K31/454 ,  C07D403/04

CPC classification number: A61K31/496 ,  C07D209/08 ,  C07D213/74 ,  C07D215/40 ,  C07D231/12 ,  C07D233/56 ,  C07D239/42 ,  C07D241/04 ,  C07D241/20 ,  C07D249/08 ,  C07D261/20 ,  C07D295/14 ,  C07D295/155 ,  C07D307/66 ,  C07D307/68 ,  C07D317/58 ,  C07D333/58 ,  C07D333/66 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D471/06 ,  C07D495/04 ,  C07D498/04

Abstract: The invention relates to heterocyclic substituted carbonyl derivatives that display selective binding to dopamine D3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D3 receptors.

Abstract translation: 本发明涉及显示与多巴胺D 3受体的选择性结合的杂环取代的羰基衍生物。 另一方面，本发明涉及在需要这种治疗的患者中治疗与多巴胺D 3 N 3受体活性相关的中枢神经系统障碍的方法，包括向所述受试者施用治疗有效量的所述 用于缓解这种病症的化合物。 可能用这些化合物治疗的中枢神经系统疾病包括心理障碍，物质依赖性，物质滥用，运动障碍（例如帕金森病，帕金森综合征，神经灵敏诱导的迟发性运动障碍，杜氏综合征和亨廷顿疾病），痴呆，焦虑 疾病，睡眠障碍，昼夜节律紊乱和情绪障碍。 本发明还涉及制备本文所述化合物的方法以及制备和使用化合物作为多巴胺D 3受体的显像剂的方法。

公开(公告)号：US20070049573A1

公开(公告)日：2007-03-01

申请号：US11467277

申请日：2006-08-25

Applicant: Armin BAUER ,  Michael WAGNER ,  Marc NAZARE ,  Volkmar WEHNER ,  Matthias URMANN ,  Hans MATTER

Inventor： Armin BAUER ,  Michael WAGNER ,  Marc NAZARE ,  Volkmar WEHNER ,  Matthias URMANN ,  Hans MATTER

IPC: A61K31/553 ,  A61K31/55 ,  A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/52 ,  A61K31/4709 ,  A61K31/405 ,  A61K31/4025

CPC classification number: C07D401/12 ,  C07D401/14 ,  C07D413/14

Abstract: The present invention relates to compounds of the formulae (I) and (Ia), wherein R0; R1; R3; R4; R22, Q; V, G and M have the meanings indicated in the claims. The compounds of the formulae (I) and (Ia) are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formulae (I) and (Ia), their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Abstract translation: 本发明涉及式（I）和（Ia）的化合物，其中R 0， R＆lt; 1＆gt;; R3; R4; R22，Q; V，G和M具有权利要求中所示的含义。 式（I）和（Ia）的化合物是有价值的药理活性化合物。 它们具有强烈的抗血栓形成作用，适用于治疗和预防心血管疾病如血栓栓塞性疾病或再狭窄。 它们是血液凝固酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆抑制剂，并且通常可用于存在因子Xa和/或因子VIIa的不期望活性或用于治愈 或预防因子Xa和/或因子VIIa的抑制。 本发明还涉及制备式（I）和（Ia）化合物的方法，其用途，特别是作为药物中的活性成分，以及包含它们的药物制剂。

公开(公告)号：US08344004B2

公开(公告)日：2013-01-01

申请号：US12796886

申请日：2010-06-09

Applicant: Karl Schoenafinger ,  Stefanie Keil ,  Matthias Urmann ,  Hans Matter ,  Maike Glien ,  Wolfgang Wendler ,  Ulrike Wendler, legal representative

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

IPC: A61K31/4439 ,  A61K31/433 ,  C07D417/12

CPC classification number: C07D417/12

Abstract: The invention relates to cyclic N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides and to their physiologically acceptable salts and physiologically functional derivatives showing PPARdelta or PPARdelta and PPARgamma agonist activity.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 resistance is involved and demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

Abstract translation: 本发明涉及环状N- [1,3,4] - 噻二唑-2-基 - 苯磺酰胺及其生理上可接受的盐和生理功能衍生物，其显示出PPARdta或PPARδ和PPARγ激动剂活性。 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。 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：US08283476B2

公开(公告)日：2012-10-09

申请号：US12644371

申请日：2009-12-22

Applicant: Nis Halland ,  Marc Nazare ,  Andreas Lindenschmidt ,  Jorge Alonso ,  Omar Rkyek ,  Matthias Urmann

Inventor： Nis Halland ,  Marc Nazare ,  Andreas Lindenschmidt ,  Jorge Alonso ,  Omar Rkyek ,  Matthias Urmann

IPC: C07D231/56

CPC classification number: C07D231/56

Abstract: The present invention relates to a process for the regioselective synthesis of compounds of the formula I, wherein R0; R1; R2; R3; R4; R5; A1; A2; A3; A4, Q and J have the meanings indicated in the claims. The present invention provides a direct transition metal catalyzed process to a wide variety of multifunctional 2H-indazoles or 2H-azaindazoles of the formula (I) from 2-halo-phenylacetylenes or (2-sulfonato)phenylacetylenes and monosubstituted hydrazines.

Abstract translation: 本发明涉及一种用于区域选择性合成式I化合物的方法，其中R 0; R1; R2; R3; R4; R5; A1; A2; A3; A4，Q和J具有权利要求中所示的含义。 本发明提供了对2-卤代苯基乙炔或（2-磺酸基）苯基乙炔和单取代肼的多种式（I）的多官能2H-吲唑或2H-氮杂吲唑的直接过渡金属催化方法。

公开(公告)号：US07834030B2

公开(公告)日：2010-11-16

申请号：US12055764

申请日：2008-03-26

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

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

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

CPC classification number: C07D417/14 ,  C07D277/24 ,  C07D417/12

Abstract: 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.

Abstract translation: 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：US07772257B2

公开(公告)日：2010-08-10

申请号：US12566179

申请日：2009-09-24

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

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

IPC: A61K31/433 ,  A61K31/44

CPC classification number: C07D417/12 ,  C07D285/135

Abstract: 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 preparation of compounds 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.

Abstract translation: 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。 还公开了制备化合物的方法。 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：US07741341B2

公开(公告)日：2010-06-22

申请号：US10849436

申请日：2004-05-19

Applicant: Marc Nazare ,  Michael Wagner ,  Volkmar Wehner ,  Hans Matter ,  Matthias Urmann ,  Kurt Ritter

Inventor： Marc Nazare ,  Michael Wagner ,  Volkmar Wehner ,  Hans Matter ,  Matthias Urmann ,  Kurt Ritter

IPC: A61K31/4523 ,  C07D401/14 ,  C07D409/14

CPC classification number: C07D235/24 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D473/08 ,  C07D495/04

Abstract: The present invention relates to compounds of the formula I, wherein R0, R1, R2, Q, V, G and M are as defined herein. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Abstract translation: 本发明涉及式I化合物，其中R 0，R 1，R 2，Q，V，G和M如本文所定义。 式I的化合物是有价值的药理活性化合物。 它们具有强烈的抗血栓形成作用，并且适用于例如治疗和预防心血管疾病如血栓栓塞性疾病或再狭窄。 它们是血液凝固酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆抑制剂，并且通常可用于存在因子Xa和/或因子VIIa的不期望活性或用于治愈 或预防因子Xa和/或因子VIIa的抑制。 本发明还涉及式I化合物的制备方法，其用途，特别是作为药物中的活性成分，以及包含它们的药物制剂。

公开(公告)号：US07709481B2

公开(公告)日：2010-05-04

申请号：US12055780

申请日：2008-03-26

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

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

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

CPC classification number: C07D417/12 ,  C07D417/14

Abstract: 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.

Abstract translation: 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。