公开(公告)号：US08669266B2

公开(公告)日：2014-03-11

申请号：US12573551

申请日：2009-10-05

申请人： Marc Nazare ,  Gernot Zech ,  Melitta Just ,  Tilo Weiss ,  Gerhard Hessler ,  Joerg Czech

发明人： Marc Nazare ,  Gernot Zech ,  Melitta Just ,  Tilo Weiss ,  Gerhard Hessler ,  Joerg Czech

IPC分类号： A01N43/42 ,  A61K31/44

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

摘要： The present invention relates to compounds of the formula I, in which R1; R2; R3; R4; R5; R6; Z; A; B; E; X; Q; J; 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 anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable e.g. for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 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.

摘要翻译： 本发明涉及式I化合物，其中R 1; R2; R3; R4; R5; R6; Z; 一个; B; E; X; Q; J; 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。 它们对血小板表现出强烈的抗凝集作用，因此表现出抗血栓形成的作用， 用于治疗和预防心血管疾病如血栓栓塞性疾病或再狭窄。 它们是血小板ADP受体P2Y12的可逆拮抗剂，并且通常可用于其中存在血小板ADP受体P2Y12的不期望的活化或用于治疗或预防血小板ADP受体P2Y12的抑制的条件 。 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：US08188282B2

公开(公告)日：2012-05-29

申请号：US12353271

申请日：2009-01-14

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

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

IPC分类号： C07D513/02 ,  C07D235/00

CPC分类号： C07D235/10 ,  C07D235/08 ,  C07D235/16 ,  C07D401/04 ,  C07D471/04

摘要： 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.

摘要翻译： 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：US08026375B2

公开(公告)日：2011-09-27

申请号：US12576339

申请日：2009-10-09

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

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

IPC分类号： C07D471/04 ,  C07D209/04

CPC分类号： C07D209/08

摘要： The present invention relates to a process for the regioselective synthesis of compounds of the formula I, wherein R0; R1; R2; R3; R4; R5; R6; A1; A2; A3; A4, Q, T 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 N-aminoindole or N-amino-azaindoles of the formula I from 2-halo-phenylacetylenes or (2-sulfonato)phenyl-acetylenes and N,N-disubstituted hydrazines, useful for the production of pharmaceuticals, diagnostic agents, liquid crystals, polymers, herbicides, fungicidals, nematicidals, parasiticides, insecticides, acaricides and arthropodicides.

摘要翻译： 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; R6; A1; A2; A3; A4，Q，T和J具有权利要求中所示的含义。 本发明提供了从2-卤代 - 苯基乙炔或（2-磺酸根合）苯基 - 乙炔和N，N-二取代的，由式I表示的多种多官能N-氨基吲哚或N-氨基 - 氮杂吲哚的直接过渡金属催化方法 肼，可用于生产药物，诊断剂，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：US07465806B2

公开(公告)日：2008-12-16

申请号：US11467277

申请日：2006-08-25

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

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

IPC分类号： C07D261/06 ,  C07D207/32

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D413/14

摘要： 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.

摘要翻译： 本发明涉及式I和Ia的化合物，其中R 0; R1; 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：US08283476B2

公开(公告)日：2012-10-09

申请号：US12644371

申请日：2009-12-22

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

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

IPC分类号： C07D231/56

CPC分类号： C07D231/56

摘要： 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.

摘要翻译： 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：US07741341B2

公开(公告)日：2010-06-22

申请号：US10849436

申请日：2004-05-19

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

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

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

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

摘要： 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.

摘要翻译： 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：US20090203912A1

公开(公告)日：2009-08-13

申请号：US12353271

申请日：2009-01-14

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

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

IPC分类号： C07D471/04 ,  C07D235/08

CPC分类号： C07D235/10 ,  C07D235/08 ,  C07D235/16 ,  C07D401/04 ,  C07D471/04

摘要： 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.

摘要翻译： 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：US20080167346A1

公开(公告)日：2008-07-10

申请号：US11940654

申请日：2007-11-15

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

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

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

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

摘要： 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.

摘要翻译： 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：US07358268B2

公开(公告)日：2008-04-15

申请号：US10728339

申请日：2003-12-04

申请人： Marc Nazare ,  Armin Bauer ,  Volkmar Wehner ,  David W. Will ,  Hans Matter ,  Michael Wagner ,  Herman Schreuder

发明人： Marc Nazare ,  Armin Bauer ,  Volkmar Wehner ,  David W. Will ,  Hans Matter ,  Michael Wagner ,  Herman Schreuder

IPC分类号： A61K31/42 ,  C07D261/04 ,  C07D413/04

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14

摘要： This invention is directed to the compound of formula (I) which is useful for inhibiting the activity of Factor Xa. The present invention is also directed to compositions containing said compounds, processes for their preparation, their use, such as in inhibiting the formation of thrombin or for therapeutically or prophylactically treating a patient suffering from, or subject to, or associated with a disease state associated with a cardiovascular disorder.

摘要翻译： 本发明涉及可用于抑制因子Xa的活性的式（I）化合物。 本发明还涉及包含所述化合物的组合物，其制备方法，其用途，例如抑制凝血酶的形成或用于治疗或预防性地治疗患有或与疾病状态有关的患者或与之相关的患者 伴有心血管疾病。

公开(公告)号：US20070179122A1

公开(公告)日：2007-08-02

申请号：US11469513

申请日：2006-09-01

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

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

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

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

摘要： 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.

摘要翻译： 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。