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Oga inhibitor compounds

A compound and composition technology, applied in the field of O-GlcNAc hydrolase inhibitors, can solve problems such as glycogen mobilization defect and cell cycle arrest

Inactive Publication Date: 2019-09-20
JANSSEN PHARMA NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Oga deletion has resulted in defects in glycogen mobilization in pups and it caused genomic instability-associated cell cycle arrest in MEFs derived from homozygous knockout embryos

Method used

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Embodiment Construction

[0043] The present invention relates to compounds of formula (I) as defined above and to pharmaceutically acceptable addition salts and solvates thereof. Compounds of formula (I) are inhibitors of O-GlcNAc hydrolase (OGA) and are useful for the prophylaxis or treatment of tauopathies, in particular tauopathies selected from the group consisting of: Alzheimer progressive supranuclear palsy, Down syndrome, frontotemporal dementia, frontotemporal dementia with parkinsonism-17, Pick's disease, corticobasal degeneration, and argyrophilic granular disease; or available For the prevention or treatment of neurodegenerative diseases associated with tauopathies, especially neurodegenerative diseases selected from amyotrophic lateral sclerosis or frontotemporal dementia caused by C9ORF72 mutations.

[0044] In a particular embodiment, the invention relates to compounds of formula (I) as mentioned herein, and tautomeric and stereoisomeric forms thereof, wherein m is 1 and n is 0 or 1, In...

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Abstract

The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors of Formulas (I) and (II). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations.

Description

technical field [0001] The present invention relates to O-GlcNAc hydrolase (OGA) inhibitor having the structure shown in formula (I) [0002] [0003] wherein these groups are as defined in the specification. The present invention also relates to pharmaceutical compositions comprising such compounds, to processes for the preparation of such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, Such disorders are for example tauopathies, especially Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by tauopathies, especially amyotrophic lateral sclerosis or frontal sclerosis caused by C9ORF72 mutations temporal lobe dementia. Background technique [0004] O-GlcNAcylation is a reversible modification of proteins in which N-acetyl-D-glucosamine residues are transferred to the hydroxyl groups of serine and threonine r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/10
CPCA61P25/00A61P25/16A61P25/28A61P43/00C07D487/10
Inventor J.M.巴托洛梅-内布瑞达A.A.特拉班科-苏阿瑞兹C.M.马丁内斯维图罗
Owner JANSSEN PHARMA NV
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