Amide Compounds as RORγ Antagonists for Autoimmune Disease Treatment
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Solution Overview
Problem
Current treatments for autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, and others related to Th17 cell activity are limited in efficacy and specificity, particularly in inhibiting RORγ and its downstream effects on IL-17 production.
Innovation Solution
Development of amide compounds that act as RORγ antagonists, specifically designed to inhibit RORγ activity, thereby reducing Th17 cell differentiation and IL-17 production, which are used in pharmaceutical compositions for treating autoimmune, allergic, and metabolic diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for autoimmune diseases are used, then disease management is maintained, but efficacy and specificity in inhibiting RORγ and IL-17 production are limited
Solution Approach 1:
The patent applies parameter changes by developing novel amide compounds with specific molecular structures (formula I) that optimize the binding affinity to RORγ. By modifying chemical parameters such as substituent groups (R1-R6, R11-R16, R21-R26) on the core structure, the invention achieves enhanced inhibition efficacy and specificity for RORγ compared to existing treatments
Solution Approach 2:
The patent employs composite materials by creating amide compounds that combine multiple functional groups and structural elements into a single molecule. The composite structure includes a core framework with various substituent groups that work synergistically to achieve both high efficacy in RORγ inhibition and specificity for the target receptor
2Reliability
If RORγ inhibition is enhanced to improve therapeutic effect, then disease treatment efficacy increases, but potential off-target effects and side effects may increase
Solution Approach 1:
The patent applies local quality by designing amide compounds where specific substituent groups at particular positions on the molecular structure confer selective binding to RORγ. The localized modification of functional groups (e.g., specific arrangements of R1-R6, R11-R16) ensures that the compound interacts preferentially with RORγ while minimizing interactions with other nuclear receptors or cellular components
Solution Approach 2:
The patent uses the amide compound structure as an intermediary that selectively mediates the inhibition of RORγ. The molecular design includes specific structural features that act as intermediaries to achieve selective binding to RORγ's ligand-binding domain, thereby reducing off-target effects while maintaining therapeutic efficacy
Data Source
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AI summary
A compound of formula [I-W]: wherein each symbol is as defined in the description, or a pharmaceutically acceptable salt thereof.