Benzothiazol Compounds Inhibiting c-abl Kinase for Neurodegenerative Disorders
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and multiple system atrophy lack effective inhibitors for c-abl kinase, which contributes to disease progression.
Innovation Solution
Development of a compound with c-abl kinase inhibitory activity, specifically a compound of Formula (I) or its pharmaceutically acceptable salts, for use in pharmaceutical compositions to treat or prevent neurodegenerative disorders by administering a therapeutically effective amount to a subject in need.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for neurodegenerative disorders are used, then existing therapeutic options are limited, but c-abl kinase activity remains un inhibited leading to disease progression
Solution Approach 1:
The patent segments the therapeutic approach by specifically targeting c-abl kinase activity with dedicated inhibitors (compounds of Formula I), separating this mechanism from existing neurodegenerative disorder treatments. This allows selective inhibition of c-abl kinase to address α-synuclein pathology while maintaining other therapeutic avenues.
Solution Approach 2:
The patent introduces c-abl kinase inhibitors as an intermediary mechanism between existing treatments and disease progression. These compounds mediate therapeutic effect by specifically blocking c-abl kinase activity, which in turn prevents α-synuclein phosphorylation and aggregation, bridging the gap between current limited options and effective disease modification.
2Ease of manufacture
If c-abl kinase activity is not inhibited, then existing treatments can be administered, but α-synuclein aggregation and disease progression continue unchecked
Solution Approach 1:
The patent converts the harmful effect of c-abl kinase activity (which drives α-synuclein phosphorylation and aggregation) into a beneficial therapeutic target. By designing inhibitors that specifically block c-abl kinase, the harmful phosphorylation event is prevented, transforming the pathological mechanism into a treatable pathway.
Solution Approach 2:
The patent changes the biochemical parameter of c-abl kinase activity from active to inhibited state using compounds of Formula I. This parameter change prevents the downstream pathological events of α-synuclein phosphorylation and aggregation, thereby stopping disease progression while maintaining treatability.
3Adaptability or versatility
If c-abl kinase inhibitors are developed, then new therapeutic mechanisms are available, but the complexity of targeting specific kinase activity increases
Solution Approach 1:
The patent applies local quality by designing compounds of Formula I with specific structural features that confer selective binding to c-abl kinase. The molecular structure incorporates specific substituents and core moieties that interact with unique residues in the c-abl kinase active site, achieving local specificity without requiring complex multi-component systems.
Solution Approach 2:
The patent employs asymmetry in the molecular design of c-abl kinase inhibitors, where the compounds exhibit specific chiral centers and asymmetric substitution patterns that enable selective binding to the asymmetric active site of c-abl kinase. This asymmetric design provides high specificity while maintaining structural simplicity.
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present disclosure provides a compound of general Formula (I) having c-abl kinase inhibitory activity or pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the compound, and a method useful to treat or prevent neurodegenerative diseases using the compound.