Probiodrug Ag

Astrazeneca Ab

Ingenium Pharmaceuticals Gmbh

Andre Johannes Niestroj

Ulrich Heiser

Hans-Ulrich Demuth

Mirko Buchholz

Stephan Schilling

Torsten Hoffmann

Michael Thormann

Andreas Treml

Daniel Ramsbeck

Lutz Zeitlmann

Michael Altmstetter

Ulf-Torsten Gaertner

Torsten Hoffman

Susanne Aust

The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, wherein

Inhibitors of glutaminyl cyclase

Compounds of general Formula (I): wherein R, R, R, R, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

Inhibitors of protein kinases

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

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

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

The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, 

The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

Compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt or solvate thereof, including all tautomers, stereoisomers and polymorphs thereof wherein:

Inhibitors

The present invention provides 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.

Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases

Compounds that act as inhibitors of QC including those represented by the general formulae 1 to 9: and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Corea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

The present invention relates to DP IV-inhibitors of formula (1) for the treatment and/or prophylaxis of diseases of mammals including cancer and tumors, metastasis and tumor colonization; and metabolic diseases.

Cyclopropyl-fused pyrrolidine derivatives as dipeptidyl peptidase IV inhibitors

The present invention relates to novel inhibitors of prolyl endopeptidase of formula (1) wherein I, A, X, Y and Z are specified in the description. The compounds are useful for the treatment of diseases such as mild cognitive impairment (MCI), Alzheimer's disease, Down Syndrome, Parkinson disease and Chorea Huntington.

Inhibitors of prolyl endopeptidase

The present invention provides novel physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC, methods for screeing 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.

Growing community of inventors

Sennewitz, Germany

Andre Johannes Niestroj