Tricyclic Sulfone RORγ Modulators for IL-17 Regulation
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Solution Overview
Problem
Current therapeutic agents are inadequate in addressing the unmet medical need for treating inflammatory and autoimmune diseases, particularly those involving dysregulated IL-17 production, as seen in conditions like psoriasis, rheumatoid arthritis, and inflammatory bowel disease.
Innovation Solution
Development of tricyclic sulfone compounds that modulate the activity of the retinoid-related orphan receptor RORγ, specifically targeting RORγt, to regulate IL-17 production and mitigate immune responses associated with these diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic agents are used, then treatment of inflammatory and autoimmune diseases is provided, but the treatment is inadequate for diseases involving dysregulated IL-17 production
Solution Approach 1:
The patent employs parameter changes by developing a series of tricyclic sulfone compounds with varying substituents (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12) to optimize RORγt modulation efficacy. The structural modifications include different halogen atoms, alkyl groups, and functional groups at various positions on the tricyclic core, allowing fine-tuning of the compounds' ability to reduce IL-17 production and treat specific autoimmune and inflammatory diseases
2Reliability
If tricyclic sulfone compounds are developed to modulate RORγt, then IL-17 production is regulated, but the complexity of the compound structure increases
Solution Approach 1:
The patent applies segmentation by dividing the tricyclic sulfone compound into distinct functional modules: a core tricyclic sulfone structure (providing RORγt binding capability) and various substituent groups (R1-R12) that can be independently modified. This modular approach allows systematic optimization of efficacy while managing structural complexity through standardized building blocks
Solution Approach 2:
The patent utilizes parameter changes by systematically varying specific structural parameters (substituent types, positions, and configurations) of the tricyclic sulfone core to optimize RORγt modulation while maintaining manageable complexity through patterned modifications rather than random structural changes
Data Source
AI summary
There are described RORγ modulators of the formula (I),or stereoisomers, pharmaceutically acceptable salts thereof, wherein all substituents are defined herein.