Cbl-b Inhibitor Compounds Balancing Potency and Selectivity
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Solution Overview
Problem
There is a need for compounds that inhibit Cbl-b, a E3 ubiquitin-protein ligase acting as a negative regulator of T-cell activation, to modulate therapeutic targets for diseases and disorders.
Innovation Solution
Development of compounds of specific formulas (A-1) or (A-2) and their pharmaceutically acceptable salts, which can modulate Cbl-b activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compounds are developed to inhibit Cbl-b, then therapeutic potential for diseases and disorders is improved, but compound specificity and selectivity may worsen
Solution Approach 1:
The patent applies local quality by designing compounds with specific structural features at particular positions to enhance binding affinity for Cbl-b while maintaining selectivity. The compounds contain specific heterocyclic rings, substituent patterns, and molecular configurations at defined locations that target Cbl-b's unique structural characteristics, allowing selective inhibition without affecting other similar proteins.
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters such as heterocyclic ring types, substituent groups, chain lengths, and stereochemical configurations to optimize both potency and selectivity. By adjusting these chemical parameters across different compound embodiments, the invention achieves enhanced therapeutic potential while maintaining compound specificity through structure-activity relationship optimization.
2Ease of manufacture
If compound structure is simplified for ease of manufacture, then manufacturing precision may improve, but compound efficacy against Cbl-b may worsen
Solution Approach 1:
The patent applies segmentation by dividing the compound structure into distinct modular components including heterocyclic rings, linkers, and substituent groups that can be independently synthesized and then assembled. This modular approach allows each component to be optimized for ease of manufacture while the complete assembly maintains the necessary complexity for high Cbl-b efficacy, resolving the contradiction between manufacturing simplicity and biological activity.
Solution Approach 2:
The patent employs partial or excessive action by incorporating certain structural features that may appear more complex than necessary but ensure robust binding to Cbl-b. Some compounds include additional heterocyclic rings, extended chain lengths, or multiple substituent groups that provide excess binding affinity, ensuring efficacy is maintained even when other parts of the molecule are simplified for manufacturing purposes.
Data Source
AI summary
The present disclose includes, among other things, compounds that treat or lessen the severity of cancer, pharmaceutical compositions and methods of making and using the same.