Use of a tetrasubstituted pyrrole derivative for the preparation of a medicament for the treatment of neurodegenerative diseases

By using tetrasubstituted pyrrole derivatives to inhibit the mislocalization and aggregation of TDP-43 protein, the shortcomings of existing drugs in clearing pathological aggregates and neuroprotection were overcome, achieving significant neuroprotective and lifespan-extending effects.

CN120919117BActive Publication Date: 2026-06-09SUN YAT SEN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
SUN YAT SEN UNIV
Filing Date
2025-09-24
Publication Date
2026-06-09

AI Technical Summary

Technical Problem

Existing drugs for treating amyotrophic lateral sclerosis (ALS), such as atrasentan, have high synthesis costs and complex manufacturing processes, and their anti-neurodegenerative activity still has room for improvement. They cannot effectively clear insoluble pathological aggregates of TDP-43 protein, and existing drugs have limited neuroprotective effects against glutamate damage.

Method used

Using tetrasubstituted pyrrole derivatives of formula (I) or formula (II) or their pharmaceutically acceptable salts, TDP-43 protein is inhibited from mislocalization and aggregation by binding to glutamate receptors, promoting its return to the cell nucleus and clearing pathological aggregates, thus exhibiting higher cellular safety and neuroprotective effects.

Benefits of technology

Tetrasubstituted pyrrole derivatives significantly prolonged the lifespan of the disease model fruit flies, corrected TDP-43 nucleoplasmic misalignment, cleared insoluble pathological aggregates, and had a stronger neuroprotective effect than existing drugs.

✦ Generated by Eureka AI based on patent content.

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Abstract

The application relates to the technical field of medicines, and discloses application of a tetra-substituted pyrrole derivative in preparation of a product for treating neurodegenerative diseases. The application provides application of the tetra-substituted pyrrole derivative or a pharmaceutically acceptable salt thereof in preparation of the product for treating neurodegenerative diseases. The tetra-substituted pyrrole derivative has high cell safety, and the neuroprotective effect on glutamic acid damage is far higher than that of atrasentan, edaravone and riluzole which are standard clinical drugs; not only can the tetra-substituted pyrrole derivative effectively correct TDP-43 nuclear and cytoplasmic mislocation, but also has the ability of removing insoluble pathological aggregates which atrasentan does not have; the tetra-substituted pyrrole derivative can more effectively inhibit the co-localization of TDP-43 and stress granule protein G3BP1, and intervene in the formation of pathological granules from the source; on a whole animal model, the tetra-substituted pyrrole derivative successfully converts the advantages at the cell level into significant survival benefits, and significantly prolongs the life span of a disease model fruit fly.
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