Probiodrug Ag

Vivorian Therapeutics N.v

Robert Sommer

Ulrich Heiser

Hans-Ulrich Demuth

Torsten Hoffmann

Antje Meyer

Mirko Buchholz

Daniel Ramsbeck

Livia Boehme

Michael Thormann

Andreas Treml

Michael Almstetter

Ulf-Torsten Gaertner

Antje Hamann

Stephan Schilling

Jens-Ulrich Rahfeld

Holger Cynis

André Johannes Niestroj

Kathrin Gans

Michael Wermann

Torsten Hoffman

Astrid Kehlen

Daniel Friedrich

André J Niestroj

The invention relates to a compound of formula (I): Formula (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein A is heteraryl selected from 1H-benzimidazolyl and imidazo[1,2-a]pyridine, and R, R, R, Rand Rare as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5) and its isoenzyme glutaminyl-peptide cyclotransferase-like protein (QPCTL). QC and QPCTL catalyze 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

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 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.

Inhibitors

The invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein R, R, 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. 

Compounds of general formula (I): wherein R, R, R, R, X and Y are as defined herein are inhibitors of glutaminyl cyclase and are therefore useful in treating conditions that can be treated by modulation of glutaminyl cyclase activity.

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

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Halle/Saale, Germany

Robert Sommer