公开(公告)号：US06569849B1

公开(公告)日：2003-05-27

申请号：US08943856

申请日：1997-10-03

申请人： Tine Krogh Jorgensen ,  Rolf Hohlweg ,  Peter Madsen ,  Knud Erik Andersen ,  Svend Treppendahl ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Alexandra Silhankova ,  Karel Sindelar ,  Vladimir Valenta ,  Tomas Kalisz

发明人： Tine Krogh Jorgensen ,  Rolf Hohlweg ,  Peter Madsen ,  Knud Erik Andersen ,  Svend Treppendahl ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Alexandra Silhankova ,  Karel Sindelar ,  Vladimir Valenta ,  Tomas Kalisz

IPC分类号： A61K3155

CPC分类号： C07D401/06 ,  A61K31/445 ,  A61K31/55 ,  C07D211/60 ,  C07D401/10 ,  C07D401/12 ,  C07D403/06

摘要： The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula wherein X, Y, Z, A, R1, R2, r and s are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to secretion and circulation of insulin antagonising peptides.

摘要翻译： 本发明涉及X，Y，Z，A，R 1，R 2，r和s的一般化合物的新的N-取代的氮杂杂环化合物如本说明书的详细部分或其盐所定义，其制备方法 ，含有它们的组合物，以及其用于临床治疗疼痛，痛觉过敏和/或炎性病症的用途，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用，以及其用于治疗由 与胰岛素拮抗肽的分泌和循环有关。

公开(公告)号：US6066632A

公开(公告)日：2000-05-23

申请号：US376735

申请日：1999-08-17

申请人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

发明人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

IPC分类号： C07D211/34 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  A01N43/46 ,  A61K31/44 ,  C07D219/00 ,  C07D487/00 ,  C07D513/00

CPC分类号： C07D401/06 ,  C07D211/34 ,  C07D405/06 ,  C07D409/06

摘要： The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description, or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

摘要翻译： 本发明涉及以下通式的新的N-取代的氮杂杂环化合物：其中X，Y，Z，R 1，R 2和r如在本说明书的详细部分中所定义，或其盐，其制备方法， 含有它们的组合物，以及它们用于临床治疗疼痛，痛觉过敏和/或炎性病症的用途，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用，以及它们用于治疗由或由 胰岛素拮抗肽的分泌和循环，例如 非胰岛素依赖性糖尿病（NIDDM）和衰老相关性肥胖。

公开(公告)号：US6040318A

公开(公告)日：2000-03-21

申请号：US98579

申请日：1998-06-17

申请人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

发明人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

IPC分类号： C07D211/34 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  A01N43/40 ,  A01N43/36 ,  C07D211/06

CPC分类号： C07D401/06 ,  C07D211/34 ,  C07D405/06 ,  C07D409/06

摘要： The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description, or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to the secretion and circulation of insulin antagonizing peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

摘要翻译： 本发明涉及以下通式的新的N-取代的氮杂杂环化合物：其中X，Y，Z，R 1，R 2和r如在本说明书的详细部分中所定义，或其盐，其制备方法， 含有它们的组合物，以及它们用于临床治疗疼痛，痛觉过敏和/或炎性病症的用途，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用，以及它们用于治疗由或由 胰岛素拮抗肽的分泌和循环，例如 非胰岛素依赖性糖尿病（NIDDM）和衰老相关性肥胖。

公开(公告)号：US6060468A

公开(公告)日：2000-05-09

申请号：US943368

申请日：1997-10-03

申请人： Tine Krogh J.o slashed.rgensen ,  Erik Fischer ,  Rolf Hohlweg ,  Knud Erik Andersen ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Vladimir Valenta ,  Karel Sindelar

发明人： Tine Krogh J.o slashed.rgensen ,  Erik Fischer ,  Rolf Hohlweg ,  Knud Erik Andersen ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Vladimir Valenta ,  Karel Sindelar

IPC分类号： A61K31/4523 ,  A61K31/4535 ,  A61P3/08 ,  A61P17/04 ,  A61P25/06 ,  A61P29/00 ,  C07D405/12 ,  C07D409/12 ,  C07D411/06 ,  C07D411/12 ,  C07D491/113 ,  C07D337/14 ,  A61K31/445 ,  C07D211/90

CPC分类号： C07D405/12 ,  C07D409/12 ,  C07D411/12

摘要： The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.1a, R.sup.2, R.sup.2a, p, r and s are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to secretion and circulation of insulin antagonising peptides.

摘要翻译： 本发明涉及以下通式的新的N-取代的氮杂杂环化合物：其中X，Y，Z，R 1，R 1a，R 2，R 2a，p，r和s如在本说明书的详细部分或其盐中所定义， 其制备方法，含有它们的组合物，以及其用于临床治疗疼痛，痛觉过敏和/或炎症状况的用途，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用以及其用于治疗 由胰岛素拮抗肽分泌和循环引起或与之相关的适应症。

公开(公告)号：US6114354A

公开(公告)日：2000-09-05

申请号：US375745

申请日：1999-08-17

申请人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

发明人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

IPC分类号： C07D211/34 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D211/62 ,  A61K31/445 ,  C07D211/60

CPC分类号： C07D401/06 ,  C07D211/34 ,  C07D405/06 ,  C07D409/06

摘要： The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description, or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neuragenic pain or inflammation as well as their use for treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

摘要翻译： 本发明涉及以下通式的新的N-取代的氮杂杂环化合物：其中X，Y，Z，R 1，R 2和r如在本说明书的详细部分中所定义，或其盐，其制备方法， 含有它们的组合物，以及其用于临床治疗疼痛，痛觉过敏和/或炎性病症的用途，其中C纤维通过引发神经痛或炎症而发挥病理生理学作用，以及其用于治疗由或由 胰岛素拮抗肽的分泌和循环，例如 非胰岛素依赖性糖尿病（NIDDM）和衰老相关性肥胖。

公开(公告)号：US6100253A

公开(公告)日：2000-08-08

申请号：US376734

申请日：1999-08-17

申请人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

发明人： Knud Erik Andersen ,  Tine Krogh J.o slashed.rgensen ,  Rolf Hohlweg ,  Erik Fischer ,  Uffe Bang Olsen ,  Zdenek Polivka ,  Karel Sindelar ,  Vladimir Valenta

IPC分类号： C07D211/34 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  A61K31/55 ,  A61K31/445 ,  C07D211/06 ,  C07D307/48 ,  C07J21/00

CPC分类号： C07D401/06 ,  C07D211/34 ,  C07D405/06 ,  C07D409/06

摘要： The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description, or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

摘要翻译： 本发明涉及以下通式的新的N-取代的氮杂杂环化合物：其中X，Y，Z，R 1，R 2和r如在本说明书的详细部分中所定义，或其盐，其制备方法， 含有它们的组合物，以及它们用于临床治疗疼痛，痛觉过敏和/或炎性病症的用途，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用，以及它们用于治疗由或由 胰岛素拮抗肽的分泌和循环，例如 非胰岛素依赖性糖尿病（NIDDM）和衰老相关性肥胖。

公开(公告)号：US5916889A

公开(公告)日：1999-06-29

申请号：US943726

申请日：1997-10-03

申请人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

发明人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

IPC分类号： C07D295/06 ,  A61K31/4427 ,  A61K31/4436 ,  A61K31/444 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61P3/08 ,  A61P17/04 ,  A61P25/06 ,  A61P29/00 ,  C07D213/74 ,  C07D213/79 ,  C07D213/80 ,  C07D295/073 ,  C07D295/12 ,  C07D295/14 ,  C07D295/155 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D405/06

CPC分类号： C07D213/74 ,  C07D213/79 ,  C07D295/073 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07C2103/78

摘要： The present invention relates to 1,4-disubstituted piperazines of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for the treatment of indications caused by or related to the secretion and circulation of insulin antagonizing peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

摘要翻译： 本发明涉及以下通式的1,4-二取代哌嗪其中X，Y，Z，R 1，R 2和r如在本说明书的详细部分或其盐中所定义，其制备方法，组合物 并且用于临床治疗疼痛，痛觉过敏和/或炎性疾病，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用，以及它们用于治疗由...引起的或与之相关的适应症 胰岛素拮抗肽的分泌和循环，例如 非胰岛素依赖性糖尿病（NIDDM）和衰老相关性肥胖。

公开(公告)号：US6040302A

公开(公告)日：2000-03-21

申请号：US271565

申请日：1999-03-18

申请人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

发明人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

IPC分类号： C07D295/06 ,  A61K31/4427 ,  A61K31/4436 ,  A61K31/444 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61P3/08 ,  A61P17/04 ,  A61P25/06 ,  A61P29/00 ,  C07D213/74 ,  C07D213/79 ,  C07D213/80 ,  C07D295/073 ,  C07D295/12 ,  C07D295/14 ,  C07D295/155 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14

CPC分类号： C07D213/74 ,  C07D213/79 ,  C07D295/073 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07C2103/78

摘要： The present invention relates to 1,4-disubstituted piperazines of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for the treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

公开(公告)号：US6004961A

公开(公告)日：1999-12-21

申请号：US271785

申请日：1999-03-18

申请人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

发明人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

IPC分类号： C07D295/06 ,  A61K31/4427 ,  A61K31/4436 ,  A61K31/444 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61P3/08 ,  A61P17/04 ,  A61P25/06 ,  A61P29/00 ,  C07D213/74 ,  C07D213/79 ,  C07D213/80 ,  C07D295/073 ,  C07D295/12 ,  C07D295/14 ,  C07D295/155 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14

CPC分类号： C07D213/74 ,  C07D213/79 ,  C07D295/073 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07C2103/78

摘要： The present invention relates to 1,4-disubstituted piperazines of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for the treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

公开(公告)号：US6133268A

公开(公告)日：2000-10-17

申请号：US271564

申请日：1999-03-18

申请人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

发明人： Rolf Hohlweg ,  Peter Madsen ,  Tine Krogh J.o slashed.rgensen ,  Knud Erik Andersen ,  Brett Watson ,  Zdenek Polivka ,  Otylie Konigova ,  Martina Kovandova ,  Alexandra Silhankova ,  Vladimir Valenta

IPC分类号： C07D295/06 ,  A61K31/4427 ,  A61K31/4436 ,  A61K31/444 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61P3/08 ,  A61P17/04 ,  A61P25/06 ,  A61P29/00 ,  C07D213/74 ,  C07D213/79 ,  C07D213/80 ,  C07D295/073 ,  C07D295/12 ,  C07D295/14 ,  C07D295/155 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14

CPC分类号： C07D213/74 ,  C07D213/79 ,  C07D295/073 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07C2103/78

摘要： The present invention relates to 1,4-disubstituted piperazines of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for the treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

摘要翻译： 本发明涉及以下通式的1,4-二取代哌嗪其中X，Y，Z，R 1，R 2和r如在本说明书的详细部分或其盐中所定义，其制备方法，组合物 并且用于临床治疗疼痛，痛觉过敏和/或炎性疾病，其中C纤维通过引发神经源性疼痛或炎症而发挥病理生理学作用，以及它们用于治疗由...引起的或与之相关的适应症 胰岛素拮抗肽的分泌和循环，例如 非胰岛素依赖性糖尿病（NIDDM）和衰老相关性肥胖。