公开(公告)号：WO2008128983A1

公开(公告)日：2008-10-30

申请号：PCT/EP2008/054712

申请日：2008-04-18

Applicant: PROBIODRUG AG ,  BUCHHOLZ, Mirko ,  HEISER, Ulrich ,  HOFFMANN, Torsten ,  BÖHME, Livia

Inventor： BUCHHOLZ, Mirko ,  HEISER, Ulrich ,  HOFFMANN, Torsten ,  BÖHME, Livia

IPC: C07D233/54 ,  C07D235/06 ,  A61K31/4164 ,  A61K31/4184 ,  A61P25/00 ,  C07D405/12 ,  C07D417/12

CPC classification number: C07D233/61 ,  C07D233/64 ,  C07D235/06 ,  C07D405/12 ,  C07D417/12

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein: A represents formula (A) or formula (B) and B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Z are as defined throughout the description and the claims.

Abstract translation: 本发明涉及式（I）化合物，其用于疾病治疗的组合和用途，或其药学上可接受的盐，溶剂化物或多晶型物，包括所有互变异构体和立体异构体，其中：A表示式（A）或式（B） 和B，R 1，R 2，R 3，R 4，R 5， SUP>，R 6和Z如在整个说明书和权利要求书中所定义。

公开(公告)号：WO2006089658A2

公开(公告)日：2006-08-31

申请号：PCT/EP2006/001310

申请日：2006-02-14

Applicant: F. HOFFMANN-LA ROCHE AG ,  HOFFMANN, Torsten ,  SCHNIDER, Patrick

Inventor： HOFFMANN, Torsten ,  SCHNIDER, Patrick

IPC: C07D213/75 ,  A61K31/44 ,  A61P25/18

CPC classification number: C07D213/75 ,  C07D213/82

Abstract: The present invention relates to compounds of the formula (I), wherein R 1 /R 1’ are hydrogen or methyl; X is -C(O)N(CH 3 )- or -N(CH 3 )C(O)-; and to pharmaceutically acceptable acid addition salts thereof for the treatment of numerous inflammatory conditions, migraine, rheumatoid arthritis, asthma, inflammatory bowel disease, mediation of the emetic reflex, Parkinson's disease, anxiety, depression, psychosis, motion sickness, induced vomiting, pain, headache, migraine, Alzheimer's disease, multiple sclerosis, attenuation of morphine withdrawal, cardiovascular changes, oedema, such as oedema caused by thermal injury, chronic inflammatory diseases such as rheumatoid arthritis, asthma/bronchial hyperreactivity and other respiratory diseases including allergic rhinitis, inflammatory diseases of the gut including ulcerative colitis and Crohn's disease, ocular injury and ocular inflammatory diseases, traumatic brain injury, motion sickness, emesis and psychoimmunologic or psychosomatic disorders.

Abstract translation: 本发明涉及式（I）化合物，其中R 1，R 2，R 1，R 2， X是-C（O）N（CH 3） - 或-N（CH 3）C（O） - ; 以及其药学上可接受的酸加成盐，用于治疗许多炎性病症，偏头痛，类风湿性关节炎，哮喘，炎症性肠病，呕吐反射调节，帕金森病，焦虑症，抑郁症，精神病，运动病，诱导性呕吐，疼痛， 头痛，偏头痛，阿尔茨海默病，多发性硬化，吗啡戒断减轻，心血管改变，水肿，如热损伤引起的水肿，慢性炎性疾病如类风湿性关节炎，哮喘/支气管高反应性和其他呼吸系统疾病，包括过敏性鼻炎，炎性疾病 的肠道，包括溃疡性结肠炎和克罗恩病，眼部损伤和眼部炎症性疾病，创伤性脑损伤，运动病，呕吐和心理免疫或心身疾病。

公开(公告)号：WO2005074983A2

公开(公告)日：2005-08-18

申请号：PCT/EP2005/000653

申请日：2005-01-24

Applicant: SOFOTEC GMBH & CO. KG ,  MAUS, Joachim ,  PETZOLD, Ursula ,  SZELENYI, Istvan ,  HOFFMANN, Torsten ,  WEINGART, Mario

Inventor： MAUS, Joachim ,  PETZOLD, Ursula ,  SZELENYI, Istvan ,  HOFFMANN, Torsten ,  WEINGART, Mario

IPC: A61K39/00

CPC classification number: A61K45/06 ,  A61K31/401 ,  A61K31/519 ,  A61K31/55 ,  A61K31/573 ,  A61K2300/00

Abstract: The present invention provides novel combinations comprising a topical anticholinergic drug alone or in combination with topically administered antihistamines, topically or orally administered phosphodiesterase 4 inhibitors or topical corticosteroids for the treatment of rhinitis of various origins. It further comprises presentation of these combinations in locally applied formulations and includes various pharmaceutical formulations suitable for topical application, e.g. nasal sprays, nasal drops, emulsions, pastes, creams and gels.

Abstract translation: 本发明提供新颖的组合，其包括单独的局部抗胆碱能药物或局部施用的抗组胺剂，局部或口服给予的磷酸二酯酶4抑制剂或局部皮质类固醇用于治疗各种原因的鼻炎。 其还包括在局部施用的制剂中呈现这些组合，并且包括适用于局部应用的各种药物制剂，例如。 鼻喷雾剂，滴鼻剂，乳剂，糊剂，霜剂和凝胶剂。

公开(公告)号：WO2005039548A2

公开(公告)日：2005-05-06

申请号：PCT/EP2004/011630

申请日：2004-10-15

Applicant: PROBIODRUG AG ,  SCHILLING, Stephan ,  HOFFMANN, Torsten ,  NIESTROJ, André, Johannes ,  DEMUTH, Hans-Ulrich ,  HEISER, Ulrich

Inventor： SCHILLING, Stephan ,  HOFFMANN, Torsten ,  NIESTROJ, André, Johannes ,  DEMUTH, Hans-Ulrich ,  HEISER, Ulrich

IPC: A61K31/00

CPC classification number: A61K31/00 ,  A61K31/13 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4184 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2003072556A1

公开(公告)日：2003-09-04

申请号：PCT/EP2002/007124

申请日：2002-06-27

Applicant: PROBIODRUG AG ,  DEMUTH, Hans-Ulrich ,  HOFFMANN, Torsten ,  HEISER, Ulrich

Inventor： DEMUTH, Hans-Ulrich ,  HOFFMANN, Torsten ,  HEISER, Ulrich

IPC: C07D277/04

CPC classification number: C07D295/185 ,  A61K38/04 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  C07D207/04 ,  C07D277/04 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C07K7/06

Abstract: The present invention provides a compound of the formula (I): wherein X = CH 2 or S or a pharmaceutically acceptable salt thereof. Such compounds and their corresponding pharmaceutically acceptable acid addition salt forms, are useful in treating conditions mediated by DPIV or DPIV-like enzymes, such as arthritis, obesity, immune and autoimmune disorders, allograft transplantation, cancer, neuronal disorders and dermal diseases.

Abstract translation: 本发明提供式（I）的化合物：其中X = CH 2或S或其药学上可接受的盐。 这些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DPIV或DPIV样酶介导的病症，例如关节炎，肥胖症，免疫和自身免疫性疾病，同种异体移植，癌症，神经元疾病和皮肤疾病。

公开(公告)号：WO2003063903A3

公开(公告)日：2003-08-07

申请号：PCT/EP2003/001044

申请日：2003-02-03

Applicant: PROBIODRUG AG ,  HOFFMANN, Torsten ,  HILDEBRANDT, Martin ,  DEMUTH, Hans-Ulrich

Inventor： HOFFMANN, Torsten ,  HILDEBRANDT, Martin ,  DEMUTH, Hans-Ulrich

IPC: A61K38/55 ,  A61K31/40 ,  A61P37/06

Abstract: The present invention discloses a method for therapeutically treating mammals, including but not limited to humans, to modulate immune responses via modulation of surface expression of co-stimulatory antigens on T lymphocytes. oral administration of a DP IV inhibitor causes a potent immunosuppressive effect. This immunosuppressive effect of DP IV inhibitors is exerted by an enhancement of CTLA-4 surface expression, with simultaneous inhibition of CD28 surface expression, on T cells. Furthermore, the present invention discloses preparation of a medicament, comprising one or more inhibitors of dipeptidyl peptidase enzymatic activity, for the treatment of immune disorders such as allograft rejection or autoimmune disease.

公开(公告)号：WO2003002596A2

公开(公告)日：2003-01-09

申请号：PCT/EP2002/007133

申请日：2002-06-27

Applicant: PROBIODRUG AG ,  DEMUTH, Hans-Ulrich ,  HOFFMANN, Torsten ,  HEISER, Ulrich ,  GLUND, Konrad ,  VAN HÖRSTEN, Stephan

Inventor： DEMUTH, Hans-Ulrich ,  HOFFMANN, Torsten ,  HEISER, Ulrich ,  GLUND, Konrad ,  VAN HÖRSTEN, Stephan

IPC: C07K7/08

CPC classification number: C07D295/185 ,  A61K38/04 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  C07D207/04 ,  C07D277/04 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/081 ,  C07K5/0812 ,  C07K7/06

Abstract: The present invention provides a new use of DPIV-inhibitors. The compounds of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, are useful in treating conditions mediated by DPIV or DPIV-Iike 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.

Abstract translation: 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DPIV或DPIV-Iike酶介导的病症，例如选自中风，肿瘤的免疫，自身免疫或中枢神经系统疾病 ，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。

公开(公告)号：WO2013024043A2

公开(公告)日：2013-02-21

申请号：PCT/EP2012/065724

申请日：2012-08-10

Applicant: PROBIODRUG AG ,  GRAUBNER, Sigrid ,  JAGLA, Wolfgang ,  SCHILLING, Stephan ,  CYNIS, Holger ,  HOFFMANN, Torsten ,  WERMANN, Michael ,  SCHULZ, Katrin ,  BAEUSCHER, Christoph ,  KOHLMANN, Stefanie ,  DEMUTH, Hans-Ulrich

Inventor： GRAUBNER, Sigrid ,  JAGLA, Wolfgang ,  SCHILLING, Stephan ,  CYNIS, Holger ,  HOFFMANN, Torsten ,  WERMANN, Michael ,  SCHULZ, Katrin ,  BAEUSCHER, Christoph ,  KOHLMANN, Stefanie ,  DEMUTH, Hans-Ulrich

IPC: C07K14/47 ,  C12N9/10 ,  A01K67/027

CPC classification number: A01K67/0278 ,  A01K2217/052 ,  A01K2217/15 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2267/0312 ,  C07K14/4711 ,  C12N9/104

Abstract: The present invention provides a double transgenic non-human animal, in particular a transgenic mouse encoding Qpct proteins, which have been implicated in Qpct-related diseases, and Amyloid Precursor Protein (APP). The present invention additionally provides cells and cell lines comprising transgenes encoding for Qpct and APP. The present invention further provides methods and compositions for evaluating agents that affect Qpct, for use in compositions for the treatment of Qpct-related diseases.

Abstract translation: 本发明涉及一种双转基因非人动物，特别是编码蛋白质的转基因小鼠QPCT已在与QPCT相关的疾病有牵连，和淀粉样前体蛋白（APP）。 本发明还涉及细胞和细胞系，其包含编码QPCT和APP转基因。 本发明还涉及一种用于评估影响QPCT对于用于组合物用于治疗与QPCT相关的疾病的治疗剂的方法和组合物。

公开(公告)号：WO2012049190A1

公开(公告)日：2012-04-19

申请号：PCT/EP2011/067753

申请日：2011-10-12

Applicant: F. HOFFMANN-LA ROCHE AG ,  GRETHER, Uwe ,  HEBEISEN, Paul ,  HOFFMANN, Torsten ,  ROEVER, Stephan

Inventor： GRETHER, Uwe ,  HEBEISEN, Paul ,  HOFFMANN, Torsten ,  ROEVER, Stephan

IPC: C07D213/75 ,  C07D401/12 ,  C07D403/12 ,  C07D407/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04 ,  A61K31/444 ,  A61K31/4965 ,  A61P9/00

CPC classification number: C07D213/75 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D407/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04

Abstract: The present invention relates to compounds of the formula I wherein A, R 1 to R 7 are defined in the description, and to pharmaceutically acceptable salts thereof, their manufacture, pharmaceutical compositions containing them and their use as medicaments for the treatment and/or prophylaxis of diseases which can be treated with HDL-cholesterol raising agents, such as particularly dyslipidemia, atherosclerosis and cardiovascular diseases.

Abstract translation: 本发明涉及式I化合物，其中A，R 1至R 7在说明书中定义，及其药学上可接受的盐，其制备方法，含有它们的药物组合物及其作为用于治疗和/或预防疾病的药物的用途 其可以用HDL-胆固醇升高剂治疗，例如特别是血脂异常，动脉粥样硬化和心血管疾病。

公开(公告)号：WO2011131748A3

公开(公告)日：2012-03-15

申请号：PCT/EP2011056396

申请日：2011-04-21

Applicant: PROBIODRUG AG ,  HEISER ULRICH ,  RAMSBECK DANIEL ,  HOFFMANN TORSTEN ,  BOEHME LIVIA

Inventor： HEISER ULRICH ,  RAMSBECK DANIEL ,  HOFFMANN TORSTEN ,  BOEHME LIVIA

IPC: C07D209/08 ,  A61K31/4184 ,  A61P25/00 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14

CPC classification number: C07D209/08 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14

Abstract: The invention relates to novel heterocyclic derivatives 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.

Abstract translation: 本发明涉及作为谷氨酰胺酰环化酶抑制剂的新型杂环衍生物（QC，EC 2.3.2.5）。 QC在氨释放下催化N-末端谷氨酰胺残基在焦谷氨酸（5-氧代 - 脯氨酰基，pGlu *）中的分子内环化，并且在释放水下将N-末端谷氨酸残基分子内环化成焦谷氨酸。