Cyclohexyl Sulfone RORγ Modulators for Inflammatory Disease
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Solution Overview
Problem
Current therapeutic agents are insufficient in addressing the unmet medical need for treating inflammatory and autoimmune diseases, particularly those involving dysregulated IL-17 production, which is implicated in conditions like multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel disease, and asthma.
Innovation Solution
Development of compounds that modulate RORγt activity, specifically antagonizing RORγ in cells to treat diseases by administering therapeutically effective amounts of these compounds to subjects suffering from inflammatory, autoimmune, allergic, metabolic, or cancer-related disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic agents are used to treat inflammatory and autoimmune diseases, then existing treatment protocols can be maintained, but they are insufficient to address the unmet medical need for diseases involving dysregulated IL-17 production
Solution Approach 1:
The patent introduces novel chemical compounds with specific molecular structures (formula I) that represent a parameter change from existing therapeutic agents. These compounds target RORγt with improved efficacy by changing the chemical parameters of the therapeutic agent, thereby addressing the unmet medical need for treating diseases involving dysregulated IL-17 production while maintaining reliability of treatment
2Reliability
If compounds that modulate RORγt activity are developed, then disease treatment efficacy is improved, but the complexity of the therapeutic approach increases
Solution Approach 1:
The patent employs small molecule compounds as intermediaries that selectively modulate RORγt activity. These intermediary compounds bridge the gap between the therapeutic goal (reducing IL-17 production) and the biological target (RORγt), improving disease treatment efficacy while maintaining a manageable level of therapeutic complexity through targeted molecular intervention
3Reliability
If RORγt modulation is used to reduce IL-17 production, then symptoms of inflammatory diseases are ameliorated, but specificity of target engagement must be maintained
Solution Approach 1:
The patent designs compounds with specific local structural features (substituents at defined positions in formula I) that confer selective binding to RORγt. This local quality approach ensures that the therapeutic effect is achieved through precise target engagement at the RORγt-IL-17 axis, thereby ameliorating inflammatory disease symptoms while maintaining high specificity of target engagement
Data Source
AI summary
Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.