公开(公告)号：US20100022603A1

公开(公告)日：2010-01-28

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: A61K31/41 ,  C07D285/12 ,  A61P7/12 ,  A61P25/00

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：US20090281084A1

公开(公告)日：2009-11-12

申请号：US12474838

申请日：2009-05-29

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

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

IPC: A61K31/55 ,  A61K31/541 ,  A61K31/5377 ,  A61K31/454 ,  A61K31/427 ,  A61K31/426 ,  C07D415/00 ,  C07D277/22

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

Abstract: The invention relates to phenyl-1,2,4-oxadiazolone derivatives with phenyl group and to their physiologically acceptable salts and physiologically functional derivatives showing PPARdelta agonist activity.What are 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: 本发明涉及具有苯基的苯基-1,2,4-恶二唑酮衍生物及其生理上可接受的盐和生理功能衍生物，显示出PPARδ激动剂活性。 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。 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：US20090203912A1

公开(公告)日：2009-08-13

申请号：US12353271

申请日：2009-01-14

Applicant: Jorge ALONSO ,  Andreas LINDENSCHMIDT ,  Marc NAZARE ,  Nis HALLAND ,  Omar RKYEK ,  Matthias URMANN

Inventor： Jorge ALONSO ,  Andreas LINDENSCHMIDT ,  Marc NAZARE ,  Nis HALLAND ,  Omar RKYEK ,  Matthias URMANN

IPC: C07D471/04 ,  C07D235/08

CPC classification number: C07D235/10 ,  C07D235/08 ,  C07D235/16 ,  C07D401/04 ,  C07D471/04

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 palladium catalyzed, regioselective process to a wide variety of unsymmetrical, multifunctional N-substituted benzimidazoles or azabenzimidazoles of formula I starting from 2-halo-nitroarenes and N-substituted amides useful for the production of pharmaceuticals, diagnostic agents, liquid crystals, polymers, herbicides, fungicidals, nematicidals, parasiticides, insecticides, acaricides and arthropodicides.

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。 本发明提供了直接钯催化的区域选择性方法，用于从2-卤代 - 硝基芳烃和用于制备药物，诊断剂的N-取代酰胺开始的各种不对称，多官能的取代的苯并咪唑或式I的氮杂苯并咪唑， 液晶，聚合物，除草剂，杀真菌剂，杀线虫剂，杀寄生虫剂，杀虫剂，杀螨剂和节肢动物杀虫剂。

公开(公告)号：US07550469B2

公开(公告)日：2009-06-23

申请号：US11643594

申请日：2006-12-21

Applicant: James A Hendrix ,  Joseph T Strupczewski ,  Kenneth Bordeau ,  Matthias Urmann ,  Gregory Shutske ,  Horst Hemmerle ,  John G Jurcak ,  Harpal Gill ,  Franz J Weiberth ,  Thaddeus Nieduzak ,  Sharon Anne Jackson ,  Xu-Yang Zhao ,  Paul Justin Mueller

Inventor： James A Hendrix ,  Joseph T Strupczewski ,  Kenneth Bordeau ,  Matthias Urmann ,  Gregory Shutske ,  Horst Hemmerle ,  John G Jurcak ,  Harpal Gill ,  Franz J Weiberth ,  Thaddeus Nieduzak ,  Sharon Anne Jackson ,  Xu-Yang Zhao ,  Paul Justin Mueller

IPC: A61K31/496 ,  C07D495/04 ,  C07D498/04 ,  A61K31/4525 ,  A61K31/4535 ,  A61K31/551 ,  C07D333/66 ,  C07D409/12 ,  C07D409/14 ,  C07D413/041

CPC classification number: C07D249/08 ,  C07D231/12 ,  C07D233/56 ,  C07D333/58 ,  C07D333/66 ,  C07D333/68 ,  C07D333/70 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D451/02 ,  C07D471/04 ,  C07D495/04

Abstract: The invention relates to heterocyclic substituted amide 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D3受体的选择性结合的杂环取代的酰胺衍生物。 另一方面，本发明涉及一种治疗需要这种治疗的患者中与多巴胺D3受体活性相关的中枢神经系统障碍的方法，其包括向受试者施用治疗有效量的所述化合物以减轻这种病症。 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。 本发明还涉及本文所述化合物的制备方法以及制备和使用化合物作为多巴胺D3受体的显像剂的方法。

公开(公告)号：US07521445B2

公开(公告)日：2009-04-21

申请号：US11714047

申请日：2007-03-05

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

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

IPC: A61K31/5377 ,  A61K31/454 ,  A61K31/4535 ,  A61K31/4525 ,  C07D498/04 ,  C07D413/04 ,  C07D409/04

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D3受体的选择性结合的杂环取代的羰基衍生物。 另一方面，本发明涉及一种治疗需要这种治疗的患者中与多巴胺D3受体活性相关的中枢神经系统障碍的方法，其包括向受试者施用治疗有效量的所述化合物以减轻这种病症。 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。 本发明还涉及本文所述化合物的制备方法以及制备和使用化合物作为多巴胺D3受体的显像剂的方法。

公开(公告)号：US20090012131A1

公开(公告)日：2009-01-08

申请号：US12062769

申请日：2008-04-04

Applicant: Stefanie KEIL ,  Karl SCHOENAFINGER ,  Hans MATTER ,  Matthias URMANN ,  Maike GLIEN ,  Wolfgang WENDLER ,  Hans-Ludwig SCHAEFER ,  Eugen FALK

Inventor： Stefanie KEIL ,  Karl SCHOENAFINGER ,  Hans MATTER ,  Matthias URMANN ,  Maike GLIEN ,  Wolfgang WENDLER ,  Hans-Ludwig SCHAEFER ,  Eugen FALK

IPC: A61K31/433 ,  C07D285/135 ,  A61P3/00 ,  A61P3/10

CPC classification number: C07D285/135 ,  C07D417/12

Abstract: The present invention comprises 4-Oxy-N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides, the derivatives thereof and salts thereof as well as processes for their preparation and methods for their use as pharmaceutical compositions. More specifically, the invention relates to 4-oxy-N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides and to their physiologically acceptable salts and physiologically functional derivatives that exhibit peroxisome proliferator activator receptor (PPAR) PPARalpha, PPARdelta and PPARgamma agonist activity. The compounds themselves are defined by the structure of the formula I, wherein the various unnamed substituents are defined herein. The compounds are suitable for the treatment of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistance is involved as well as demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

Abstract translation: 本发明包括4-氧基-N- [1,3,4] - 噻二唑-2-基 - 苯磺酰胺及其衍生物及其盐，以及其制备方法及其用作药物组合物的方法。 更具体地，本发明涉及4-氧-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，其表现出过氧化物酶体增殖物激活受体（PPAR）PPARα， PPARδ和PPARgamma激动剂活性。 化合物本身由式I的结构定义，其中各种未命名的取代基在本文中定义。 该化合物适用于治疗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以及中枢和周围神经系统的脱髓鞘和其它神经变性疾病。

公开(公告)号：US20080287409A1

公开(公告)日：2008-11-20

申请号：US12055793

申请日：2008-03-26

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

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

IPC: A61K31/427 ,  A61K31/454 ,  C07D413/14 ,  C07D417/14 ,  A61P3/10 ,  A61P3/00 ,  A61K31/5377 ,  C07D417/12

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

Abstract: The present invention comprises phenyl and pyridinyl 1,2,4-oxadiazolone compounds their physiologically acceptable salts and physiologically functional derivatives that exhibit peroxisome proliferator activator receptor (PPAR) delta agonist activity. Also described and claimed are processes for their preparation and their use as pharmaceuticals. These are compounds of formula I, in which the R-group substituents are defined herein. 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 de-myelinating and other neurodegenerative disorders of the central and peripheral nervous system.

Abstract translation: 本发明包括苯基和吡啶基-1,2,4-恶二唑酮化合物，其生理上可接受的盐和生理功能衍生物显示出过氧化物酶体增殖物激活受体（PPAR）δ激动剂活性。 还描述和要求保护的是其制备方法及其作为药物的用途。 这些是式I化合物，其中R基团取代基在本文中定义。 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以及中枢和周围神经系统的脱髓鞘和其它神经变性疾病。

公开(公告)号：US20080227834A1

公开(公告)日：2008-09-18

申请号：US12055771

申请日：2008-03-26

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

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

IPC: A61K31/4245 ,  C07D271/07 ,  A61P3/00

CPC classification number: C07D413/12 ,  C07D417/12

Abstract: The present invention relates to derivatives of 2-aminothiazoles and 2-aminooxazoles in all its stereoisomeric forms, enantiomeric forms and mixtures in any ratio, and its physiologically acceptable salts and tautomeric forms showing peroxisome proliferators activator receptor (PPAR) delta agonist activity. These compounds 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: 本发明涉及所有其立体异构形式的2-氨基噻唑和2-氨基恶唑衍生物，对映体形式和任何比例的混合物，以及其生理上可接受的盐和互变异构体形式，其显示过氧化物酶体增殖物激活受体（PPAR）δ激动剂活性。 这些化合物是式I化合物，其中基团如上所定义，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：US20080167346A1

公开(公告)日：2008-07-10

申请号：US11940654

申请日：2007-11-15

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

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

IPC: A61K31/4535 ,  C07C233/57 ,  A61K31/166 ,  A61P11/00 ,  A61P9/00 ,  C07D409/12

CPC classification number: C07D211/58 ,  C07D333/38 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D419/14

Abstract: The present invention relates to compounds of the formula I, which exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses.

Abstract translation: 本发明涉及式I化合物，其具有强的抗血栓形成作用，并且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。

公开(公告)号：US20070179122A1

公开(公告)日：2007-08-02

申请号：US11469513

申请日：2006-09-01

Applicant: Matthias Urmann ,  Marc Nazare ,  Volkmar Wehner ,  Hans Matter ,  Armin Bauer ,  Michael Wagner

Inventor： Matthias Urmann ,  Marc Nazare ,  Volkmar Wehner ,  Hans Matter ,  Armin Bauer ,  Michael Wagner

IPC: A61K31/553 ,  A61K31/551 ,  A61K31/55 ,  A61K31/541 ,  A61K31/496 ,  A61K31/5377 ,  C07D417/02 ,  C07D413/02 ,  C07D403/02

CPC classification number: C07K5/0202 ,  C07D265/32 ,  C07D265/33 ,  C07D291/06 ,  C07D295/112 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D419/12

Abstract: The present invention relates to compounds of the formula I, in which R0; R1; R2; R3; R4; R5, R, Q; V, G and M have the meanings indicated in the claims. 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 thromboemboic 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＆lt; 1＆gt;; R 2; 3＆lt; 3＆gt; R 4; R 5，R，Q; V，G和M具有权利要求中所示的含义。 式I的化合物是有价值的药理活性化合物。 它们表现出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。