Probiodrug Ag

Prosidion Limited

Osi Pharmaceuticals, Inc.

Vivoryon Therapeutics N.v.

Other

Meda Pharma Gmbh & Co. Kg

F. Hoffmann-la Roche Ag

Helsinn Healthcare Sa

Torsten Hoffmann

Hans-Ulrich Demuth

Ulrich Heiser

Stephan Schilling

Livia Boehme

Daniel Ramsbeck

Antje Meyer

Andre Johannes Niestroj

Robert Sommer

Dagmar Schlenzig

Patrick Schnider

Stephan Von Hoersten

Peter Mohr

David B Rozema

Heinz Stadler

Philipp Hadwiger

David L Lewis

Mirko Buchholz

Ingo Roehl

Kerstin Jahn-Hofmann

André Johannes Niestroj

Konrad Glund

Guenther Ott

Ingeborg Lues

Susanne Manhart

Uwe Grether

Stephan Roever

Paul Hebeisen

Istvan Szelenyi

Eric Argirios Kitas

Thierry Godel

Anthony P Ford

Jens-Ulrich Rahfeld

Michael Thormann

Andreas Treml

Michael Almstetter

Joachim Maus

Holger Cynis

Kathrin Gans

Ulf-Torsten Gaertner

Michael Wermann

Peter Jurgen Cnota

Mario Weingart

Antje Hamann

Ursula Petzold

Beatrix Fyrnys

Kerstin Kühn-Wache

Fred Rosche

Peter Jürgen Cnota

Sonia Maria Poli

Ullrich Munzel

Jorn Schmidt

Astrid Kehlen

Daniel Friedrich

Joachim Baer

Wolfgang Brandt

Joachim Bär

André J Niestroj

Pierre Vankan

Eric A Kitas

Susanne Buser

Andrew John Sleight

Barbara Lenz

Livia Böhme

Kerstin c/o Probiodrug Ag Kuehn-Wache

Compounds of formula (I):A-B-D-Eor a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein: These compounds of formula (I) are inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5).

Inhibitors

The invention relates to a compound of formula (I): A-B-D-E (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein: A is selected from monocyclic and bicyclic heteroaryl, which may independently substituted by alkyl or amino; B is selected from alkyl, heteroalkyl, alkyl-amino, aryl, heteroaryl, cycloalkyl, heterocyclyl and alkylene, wherein said groups may independently be substituted by alkyl; D is selected from aryl-amino, heteroaryl-amino, cycloalkyl-amino, heterocyclyl, heterocyclyl-amino, urea, thioamide, thiourea, sulfonamide, sulfoximine and sulfamoyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted; and E is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted. The compounds of formula (I) are 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.

The invention relates to novel pyrrolidine derivatives of formula (I): wherein R, Rand Rare 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.

The present invention provides a knock-out non-human animal, in particular a mouse carrying a Qpct knock-out mutation. The present invention additionally provides the respective cells and cell lines and methods and compositions for evaluating agents that affect Qpct, for use in compositions for the treatment of Qpct-related diseases.

Mouse carrying a knock-out mutation of the Qpct-gene

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.

Inhibitors of glutaminyl cyclase

The present invention relates in general to an inhibitor of a glutaminyl peptide cyclotransferase-like protein (QPCTL), and the use thereof for the treatment and/or prevention of an inflammatory disease or disorder selected from the group consisting of (a) chronic and acute inflammations, e.g. rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis; (b) other inflammatory diseases, e.g. neuropathic pain, graft rejection/graft failure/graft vasculopathy, HIV infections/AIDS, gestosis, tuberous sclerosis, Guillain-Barr&#xe9; syndrome, chronic inflammatory demyelinizing polyradiculoneuropathy and multiple sclerosis; (c) neuroinflammation; and (d) neurodegenerative diseases, e.g. mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, and Familial Danish Dementia, which may result from neuroinflammation.

Use of isoQC inhibitors in the treatment and prevention of inflammatory diseases or conditions

Provided herein are methods for treating and preventing neurodegenerative disease in a mammal by administering an inhibitor of glutaminyl cyclase (QC). Neurodegenerative diseases treatable or preventable according to methods described herein include mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, and Familial Danish Dementia.

Method for prophylactic treatment of alzheimer's disease using inhibitors of glutaminyl cyclase and glutamate cyclases

Novel physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC, methods for screening for such effectors, and the use of such effectors and pharmaceutical compositions comprising such effectors for the treatment of conditions that can be treated by modulation of QC-activity. Preferred compositions additionally comprise inhibitors of DP IV or DP IV-like enzymes for the treatment or alleviation of conditions that can be treated by modulation of QC- and DP IV-activity.

Use of inhibtors of glutaminyl cyclases for treatment and prevention of disease

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.

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/oinfections, colorectal cancer, Zolliger-Ellison syndrome, Familial British Dementia and Familial Danish Dementia.

Use of effectors of glutaminyl and glutamate cyclases

Pharmaceutical compositions comprising an anticholinergic and at least one leukotriene inhibitor for treatment of respiratory diseases, including allergic rhinitis, bronchial asthma, COPD and common cold, and methods of treatment.

Combination of anticholinergics and leukotriene receptor antagonists for the treatment of respiratory diseases

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: 

The present application relates to the secondary binding site of dipeptidyl peptidase IV, its relationship amongst substrates and to the modulation of substrate specificity of dipeptidyl peptidase IV (DP IV, synonym: DPP IV, CD26, EC 3.4.14.5). The application relates further to compounds that bind to the secondary binding site of DP IV and their use to modulate the substrate specificity of DP IV; methods of treatment of various DP IV mediated disorders; and screening methods for the identification of secondary binding sites on DP IV and DP IV-like enzymes.

Secondary binding site of dipeptidyl peptidase IV (DP IV)

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Halle/Saale, Germany

Torsten Hoffmann