Important Compound Classes
Title
OGA Inhibitors Compounds
Patent Application Number
WO 2018141984A1
Publication Date
August 8, 2018
Priority Application
EP 2017–154751
Priority Date
February 6, 2017
Inventors
Bartolome-Nebreda, J. M.; Trabanco-Suarez, A. A.; Martinez Viturro, C. M.
Assignee Company
Janssen Pharmaceutica NV, Belgium
Disease Area
Tauopathies, Alzheimer’s disease
Biological Target
O-GlcNAc hydrolase (OGA)
Summary
The present application claims a series of bicyclic spiropyrrolidines and spiropiperidines for the treatment of tauopathy including Alzheimer’s disease. The compounds described in this application are potentially useful in the treatment of a wide range of diseases such as Alzheimer’s disease, Down’s syndrome, frontotemporale lobe dementia, and Pick’s disease.
Key Structures
Biological Assay
The compounds described in this application were tested in an enzymatic assay based on the inhibition of the hydrolysis of fluorescein mono-β-d-N-acetyl-glucosamine by the recombinant human OGA. Additionally, compounds were evaluated in a cellular assay using HEK293 cells inducible for P301L mutant human Tau (isoform 2N4R). In this assay, OGA inhibition was evaluated through immunochemical detection of O-GlcNAcylated proteins by the use of a monoclonal antibody detecting O-GlcNAcylated residues.
Biological Data
Results of enzymatic and cell-based assays:
The author declares no competing financial interest.