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1. 发明授权

US07368576B2 Dipeptidyl peptidase IV inhibitors and their uses as anti-cancer agents 失效
标题翻译：二肽基肽酶IV抑制剂及其用途作为抗癌剂
公开(公告)号：US07368576B2
公开(公告)日：2008-05-06
申请号：US11481349
申请日：2006-07-05
申请人： Stephan von Hoersten , Hans-Ulrich Demuth , Torsten Hoffmann
发明人： Stephan von Hoersten , Hans-Ulrich Demuth , Torsten Hoffmann
IPC分类号： C07D277/04 , C07D277/16 , C07D277/18 , C07D291/02 , C07D291/04
CPC分类号： A61K31/401 , A61K31/426 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/55
摘要： The present invention provides new uses of DPIV-inhibitors of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, for treating conditions mediated by DPIV or DPIV-like enzymes, such as cancer and tumors. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of metastasis and tumor colonization.
摘要翻译：本发明提供本发明的DPIV-抑制剂及其相应的药学上可接受的酸加成盐形式的新用途，用于治疗由DPIV或DPIV样酶如癌和肿瘤介导的病症。在更优选的实施方案中，本发明的化合物可用于治疗转移和肿瘤定植。

2. 发明申请

US20050171025A1 Dipeptidyl peptidase IV inhibitors and their uses as anti-cancer agents 失效
标题翻译：二肽基肽酶IV抑制剂及其用途作为抗癌剂
公开(公告)号：US20050171025A1
公开(公告)日：2005-08-04
申请号：US11093991
申请日：2005-03-30
申请人： Stephan von Hoersten , Hans-Ulrich Demuth , Torsten Hoffmann
发明人： Stephan von Hoersten , Hans-Ulrich Demuth , Torsten Hoffmann
IPC分类号： A61K31/401 , A61K31/426 , A61K38/04 , A61K38/05 , A61K38/06
CPC分类号： A61K31/401 , A61K31/426 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/55
摘要： The present invention provides new uses of DPIV-inhibitors of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, for treating conditions mediated by DPIV or DPIV-like enzymes, such as cancer and tumors. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of metastasis and tumor colonization.
摘要翻译：本发明提供本发明的DPIV-抑制剂及其相应的药学上可接受的酸加成盐形式的新用途，用于治疗由DPIV或DPIV样酶如癌和肿瘤介导的病症。在更优选的实施方案中，本发明的化合物可用于治疗转移和肿瘤定植。

3. 发明授权

US07109347B2 Dipeptidyl peptidase IV inhibitors and their uses as anti-cancer agents 失效
公开(公告)号：US07109347B2
公开(公告)日：2006-09-19
申请号：US11093991
申请日：2005-03-30
申请人： Stephan von Hoersten , Hans-Ulrich Demuth , Torsten Hoffmann
发明人： Stephan von Hoersten , Hans-Ulrich Demuth , Torsten Hoffmann
IPC分类号： C07D277/04 , C07D277/16 , C07D277/18 , C07D207/00 , C07D295/00 , C07D291/00 , C07D291/02 , C07D291/04
CPC分类号： A61K31/401 , A61K31/426 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/55
摘要： The present invention provides new uses of DPIV-inhibitors of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, for treating conditions mediated by DPIV or DPIV-like enzymes, such as cancer and tumors. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of metastasis and tumor colonization.

4. 发明授权

US07368421B2 Use of dipeptidyl peptidase IV inhibitors in the treatment of multiple sclerosis 失效
标题翻译：二肽基肽酶IV抑制剂在多发性硬化症的治疗中的应用
公开(公告)号：US07368421B2
公开(公告)日：2008-05-06
申请号：US10126374
申请日：2002-04-19
申请人： Hans-Ulrich Demuth , Torsten Hoffmann , Konrad Glund , Ulrich Heiser , Stephan von Hoersten
发明人： Hans-Ulrich Demuth , Torsten Hoffmann , Konrad Glund , Ulrich Heiser , Stephan von Hoersten
IPC分类号： A61K38/00 , A61K38/02 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07K2/00 , C07K7/04 , C07K5/02 , C07K5/08 , C07K5/10
CPC分类号： C07K7/06 , A61K38/04 , A61K38/06 , A61K38/07 , A61K38/08 , C07D207/04 , C07D277/04 , C07K5/0806 , C07K5/0808 , C07K5/081 , C07K5/0812
摘要： The present invention provides a new use of DP IV-inhibitors. The compounds of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, are useful in treating conditions mediated by DP IV or DP IV-like enzymes, such as immune, autoimmune or central nervous system disorder selected from the group consisting of strokes, tumors, ischemia, Parkinson's disease and migraines. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of multiple sclerosis.
摘要翻译：本发明提供DPIV-抑制剂的新用途。本发明的化合物及其相应的药学上可接受的酸加成盐形式可用于治疗由DP IV或DP IV样酶介导的病症，例如免疫，自身免疫或中枢神经系统疾病，其选自中风，肿瘤，局部缺血，帕金森病和偏头痛。在更优选的实施方案中，本发明的化合物可用于治疗多发性硬化。

5. 发明授权

US08168199B2 Dipeptidyl peptidase IV inhibitors for the treatment of schizophrenia and depression 有权
标题翻译：二肽基肽酶IV抑制剂用于治疗精神分裂症和抑郁症
公开(公告)号：US08168199B2
公开(公告)日：2012-05-01
申请号：US12202774
申请日：2008-09-02
申请人： Hans-Ulrich Demuth , Ants Kask , Huu Phuc Nguyen , Stephan von Hoersten , Susanne Kruber , Matthias Hoffmann
发明人： Hans-Ulrich Demuth , Ants Kask , Huu Phuc Nguyen , Stephan von Hoersten , Susanne Kruber , Matthias Hoffmann
IPC分类号： A61K39/00 , A61K39/38
CPC分类号： A61K31/426 , A61K31/40 , A61K38/2271 , A61K45/06 , A61K2300/00
摘要： A method for therapeutically treating an animal, including a human, for psychosomatic, depressive and neuropsychiatric diseases, such as anxiety, depression, insomnia, schizophrenia, epilepsy, spasm and chronic pain. Administration of a suitable DP IV inhibitor causes the reduction of activity in the enzyme dipeptidyl peptidase (DP IV or CD 26) or of DP IV-like enzyme activity in the brain of mammals and leads as a causal consequence to a reduced degradation of the neuropeptide Y (NPY) and similar substrates by DP IV and DP IV-like enzymes. Such treatment will result in a reduction or delay in the decrease of the concentration of functionally active neuronal NPY (1-36). As a consequence of the resulting enhanced stability of the endogenous NPY (1-36) caused by the inhibition of DP IV activity, NPY activity is prolonged thereby resulting among other things in functionally active NPY Y1 receptor activity thereby facilitating antidepressive, anxiolytic, analgesic, antihypertension and other neurological effects.
摘要翻译：用于治疗性处理动物，包括人的用于心身，抑郁和神经精神疾病如焦虑，抑郁，失眠，精神分裂症，癫痫，痉挛和慢性疼痛的方法。施用合适的DP IV抑制剂导致哺乳动物脑中的酶二肽基肽酶（DP IV或CD 26）或DP IV样酶活性的活性降低，并导致神经肽降低的降低的因果结果 Y（NPY）和类似底物的DP IV和DP IV样酶。这种治疗将导致功能活跃的神经元NPY（1-36）的浓度降低或延迟。由于由抑制DP IV活性引起的内源性NPY（1-36）的增强的稳定性，NPY活性延长，从而导致功能活性的NPY Y1受体活性，从而促进抗抑郁，抗焦虑，止痛，抗高血压等神经功能。

6. 发明申请

US20090062203A1 DIPEPTIDYL PEPTIDASE IV INHIBITORS FOR THE TREATMENT OF SCHIZOPHRENIA AND DEPRESSION 有权
标题翻译：用于治疗精神分裂症和抑郁症的替代肽第四剂抑制剂
公开(公告)号：US20090062203A1
公开(公告)日：2009-03-05
申请号：US12202774
申请日：2008-09-02
申请人： Hans-Ulrich Demuth , Ants Kask , Huu Phuc Nguyen , Stephan von Hoersten , Susanne Kruber , Matthias Hoffmann
发明人： Hans-Ulrich Demuth , Ants Kask , Huu Phuc Nguyen , Stephan von Hoersten , Susanne Kruber , Matthias Hoffmann
IPC分类号： A61K38/17 , A61K38/05
CPC分类号： A61K31/426 , A61K31/40 , A61K38/2271 , A61K45/06 , A61K2300/00
摘要： A method for therapeutically treating an animal, including a human, for psychosomatic, depressive and neuropsychiatric diseases, such as anxiety, depression, insomnia, schizophrenia, epilepsy, spasm and chronic pain. Administration of a suitable DP IV inhibitor causes the reduction of activity in the enzyme dipeptidyl peptidase (DP IV or CD 26) or of DP IV-like enzyme activity in the brain of mammals and leads as a causal consequence to a reduced degradation of the neuropeptide Y (NPY) and similar substrates by DP IV and DP IV-like enzymes. Such treatment will result in a reduction or delay in the decrease of the concentration of functionally active neuronal NPY (1-36). As a consequence of the resulting enhanced stability of the endogenous NPY (1-36) caused by the inhibition of DP IV activity, NPY activity is prolonged thereby resulting among other things in functionally active NPY Y1 receptor activity thereby facilitating antidepressive, anxiolytic, analgesic, antihypertension and other neurological effects.
摘要翻译：用于治疗性处理动物，包括人的用于心身，抑郁和神经精神疾病如焦虑，抑郁，失眠，精神分裂症，癫痫，痉挛和慢性疼痛的方法。施用合适的DP IV抑制剂导致哺乳动物脑中的酶二肽基肽酶（DP IV或CD 26）或DP IV样酶活性的活性降低，并导致神经肽降低的降低的因果结果 Y（NPY）和类似底物的DP IV和DP IV样酶。这种治疗将导致功能活跃的神经元NPY（1-36）的浓度降低或延迟。由于由抑制DP IV活性引起的内源性NPY（1-36）的增强的稳定性，NPY活性延长，从而导致功能活性的NPY Y1受体活性，从而促进抗抑郁，抗焦虑，止痛，抗高血压等神经功能。

7. 发明授权

US07435420B2 Dipeptidyl peptidase IV inhibitors for the treatment of anxiety 有权
标题翻译：二肽基肽酶IV抑制剂治疗焦虑症
公开(公告)号：US07435420B2
公开(公告)日：2008-10-14
申请号：US11397281
申请日：2006-04-04
申请人： Stephan von Hoersten , Ants Kask , Hans-Ulrich Demuth , Huu Phuc Nguyen , Susanne Kruber , Matthias Hoffmann
发明人： Stephan von Hoersten , Ants Kask , Hans-Ulrich Demuth , Huu Phuc Nguyen , Susanne Kruber , Matthias Hoffmann
IPC分类号： A61K39/00 , A61K39/38 , A61K35/00 , A01N37/18
CPC分类号： A61K31/426 , A61K31/40 , A61K38/2271 , A61K45/06 , A61K2300/00
摘要： The present invention discloses a method for therapeutically treating an animal, including a human, for psychosomatic, depressive and neuropsychiatric diseases, such as anxiety, depression, insomnia, schizophrenia, epilepsy, spasm and chronic pain.Administration of a suitable DP IV inhibitor causes the reduction of activity in the enzyme dipeptidyl peptidase (DP IV or CD 26) or of DP IV—like enzyme activity in the brain of mammals and leads as a causal consequence to a reduced degradation of the neuropeptide Y (NPY) and similar substrates by DP IV and DP IV-like enzymes. Such treatment will result in a reduction or delay in the decrease of the concentration of functionally active neuronal NPY (1-36). As a consequence of the resulting enhanced stability of the endogenous NPY (1-36) caused by the inhibition of DP IV activity, NPY activity is prolonged thereby resulting among other things in functionally active NPY Y1 receptor activity thereby facilitating antidepressive, anxiolytic, analgesic, antihypertension and other neurological effects.
摘要翻译：本发明公开了一种治疗性处理动物（包括人）用于心身，抑郁和神经精神疾病如焦虑，抑郁，失眠，精神分裂症，癫痫，痉挛和慢性疼痛的方法。施用合适的DP IV抑制剂导致哺乳动物脑中的酶二肽基肽酶（DP IV或CD 26）或DP IV样酶活性的活性降低，并导致神经肽降低的降低的因果结果 Y（NPY）和类似底物的DP IV和DP IV样酶。这种治疗将导致功能活跃的神经元NPY（1-36）的浓度降低或延迟。由于由抑制DP IV活性引起的内源性NPY（1-36）的增强的稳定性，NPY活性延长，从而导致功能活性的NPY Y1受体活性，从而促进抗抑郁，抗焦虑，止痛，抗高血压等神经功能。

8. 发明申请

US20060252701A1 Modulation of central nervous system (CNS) dipeptidyl peptidase IV (DPIV)-like activity for the treatment of neurological and neuropsychological disorders 有权
标题翻译：调节中枢神经系统（CNS）二肽基肽酶IV（DPIV）样活性用于治疗神经和神经心理障碍
公开(公告)号：US20060252701A1
公开(公告)日：2006-11-09
申请号：US11397281
申请日：2006-04-04
申请人： Stephan von Hoersten , Ants Kask , Hans-Ulrich Demuth , Huu Nguyen , Susanne Kruber , Matthias Hoffmann
发明人： Stephan von Hoersten , Ants Kask , Hans-Ulrich Demuth , Huu Nguyen , Susanne Kruber , Matthias Hoffmann
IPC分类号： A61K38/04
CPC分类号： A61K31/426 , A61K31/40 , A61K38/2271 , A61K45/06 , A61K2300/00
摘要： The present invention discloses a method for therapeutically treating an animal, including a human, for psychosomatic, depressive and neuropsychiatric diseases, such as anxiety, depression, insomnia, schizophrenia, epilepsy, spasm and chronic pain. Administration of a suitable DP IV inhibitor causes the reduction of activity in the enzyme dipeptidyl peptidase (DP IV or CD 26) or of DP IV—like enzyme activity in the brain of mammals and leads as a causal consequence to a reduced degradation of the neuropeptide Y (NPY) and similar substrates by DP IV and DP IV-like enzymes. Such treatment will result in a reduction or delay in the decrease of the concentration of functionally active neuronal NPY (1-36). As a consequence of the resulting enhanced stability of the endogenous NPY (1-36) caused by the inhibition of DP IV activity, NPY activity is prolonged thereby resulting among other things in functionally active NPY Y1 receptor activity thereby facilitating antidepressive, anxiolytic, analgesic, antihypertension and other neurological effects.
摘要翻译：本发明公开了一种治疗性处理动物（包括人）用于心身，抑郁和神经精神疾病如焦虑，抑郁，失眠，精神分裂症，癫痫，痉挛和慢性疼痛的方法。施用合适的DP IV抑制剂导致哺乳动物脑中的酶二肽基肽酶（DP IV或CD 26）或DP IV样酶活性的活性降低，并导致神经肽降低的降低的因果结果 Y（NPY）和类似底物的DP IV和DP IV样酶。这种治疗将导致功能活跃的神经元NPY（1-36）的浓度降低或延迟。由于由抑制DP IV活性引起的内源性NPY（1-36）的增强的稳定性，NPY活性延长，从而导致功能活性的NPY Y1受体活性，从而促进抗抑郁，抗焦虑，止痛，抗高血压等神经功能。

9. 发明授权

US08486940B2 Inhibitors 有权
公开(公告)号：US08486940B2
公开(公告)日：2013-07-16
申请号：US12880369
申请日：2010-09-13
申请人： Ulrich Heiser , Daniel Ramsbeck , Robert Sommer , Antje Meyer , Torsten Hoffmann , Livia Boehme , Hans-Ulrich Demuth
发明人： Ulrich Heiser , Daniel Ramsbeck , Robert Sommer , Antje Meyer , Torsten Hoffmann , Livia Boehme , Hans-Ulrich Demuth
IPC分类号： A61K31/535 , A61K31/497 , A61K31/42 , A61K31/415 , A61K31/40 , C07D211/06 , C07D265/30 , C07D241/02 , C07D263/02 , C07D233/02
CPC分类号： C07D403/04 , A61K31/4184 , A61K31/422 , A61K31/427 , A61K31/437 , A61K31/454 , A61K31/496 , A61K31/5355 , A61K31/5377 , A61K45/06 , C07D235/06 , C07D401/14 , C07D403/14 , C07D405/14 , C07D413/04 , C07D413/14 , C07D417/04 , C07D417/14 , C07D471/04
摘要： The invention relates to novel pyrrolidine derivatives of formula (I): wherein R1, R2 and R3 are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

10. 发明申请

US20090149394A1 USE OF EFFECTORS OF GLUTAMINYL AND GLUTAMATE CYCLASES 有权
标题翻译：使用谷氨酰胺和谷氨酸周期的影响
公开(公告)号：US20090149394A1
公开(公告)日：2009-06-11
申请号：US12182113
申请日：2008-07-29
申请人： Stephan Schilling , Torsten Hoffmann , Andre Johannes Niestroj , Hans-Ulrich Demuth , Ulrich Heiser
发明人： Stephan Schilling , Torsten Hoffmann , Andre Johannes Niestroj , Hans-Ulrich Demuth , Ulrich Heiser
IPC分类号： A61K38/06 , A61K31/131 , A61K31/095 , A61K31/426 , A61K31/40 , A61P25/00 , A61K31/4439 , A61K31/472 , A61K38/05
CPC分类号： A61K31/00 , A61K31/13 , A61K31/416 , A61K31/4178 , A61K31/4184 , A61K38/06 , A61K38/07 , A61K38/08
摘要： The present invention provides novel physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC and the use of such effectors and pharmaceutical compositions comprising such effectors for the treatment of diseases that can be treated by modulation of QC-activity, e.g. diseases selected from the group consisting of duodenal cancer with or w/o Heliobacter pylori infections, colorectal cancer, Zolliger-Ellison syndrome, Familial British Dementia and Familial Danish Dementia.
摘要翻译：本发明提供了哺乳动物谷氨酰胺酰化环化酶（QC，EC 2.3.2.5）的新生理底物，QC的新效应物以及包含这些效应物的这些效应物和药物组合物的用途，用于治疗可以通过调节QC- 活动，例如选自由具有或不具有幽门螺旋杆菌感染的十二指肠癌，结肠直肠癌，佐立格 - 埃利森综合征，家族性英国痴呆和家族性丹麦痴呆组成的组的疾病。

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