AhR Modulator Scaffolds for Selective Inflammatory Disease Treatment

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Solution Overview

Problem

There is a need for potent and selective compounds that modulate Aryl hydrocarbon receptor (AhR) activity to treat various inflammatory conditions, as existing treatments are inadequate in effectively managing diseases such as inflammatory bowel disease and fibrostenosis.

Innovation Solution

Development of specific AhR-binding compounds, including those represented by Formulas I, II, III, and IV, which are administered to modulate AhR activity and treat inflammatory diseases and conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments are used for inflammatory conditions, then treatment is provided, but the treatments are inadequate in effectively managing diseases such as inflammatory bowel disease and fibrostenosis

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidsuitability for specific inflammatory conditions

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by developing compounds with specific molecular structures (Formulas I, II, III, and IV) that have optimized parameters for AhR binding affinity and selectivity. The chemical structures include specific substituents (R1-R6, Ar, X1-X4) that can be varied to tune the pharmacological properties, thereby improving treatment effectiveness for specific inflammatory conditions while maintaining broad applicability across different AhR-mediated diseases.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If potent and selective AhR-binding compounds are developed, then AhR activity is effectively modulated, but the complexity of compound design and synthesis increases

Engineering Contradiction:

Improveselectivity of AhR modulationVSAvoidcomplexity of compound structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the AhR modulator molecule into distinct functional segments: a core structural framework (tetrahydro-β-carboline, indole, or quinoline cores) and multiple substitutable positions (R1-R6, Ar, X1-X4). This segmentation allows independent optimization of each segment for binding affinity, selectivity, and pharmacokinetic properties, thereby achieving potent and selective AhR modulation while managing structural complexity through modular design.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies universality by designing a platform of compounds with a common core structure that can bind to AhR, while allowing variation in substituents to achieve different pharmacological profiles. The core structures (Formulas I, II, III, and IV) serve as universal scaffolds that can be adapted for various AhR-mediated conditions, reducing the need to design entirely new molecules for each application and thereby managing complexity while maintaining selectivity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS12577256B2Aryl receptor modulators and methods of making and using the same

Publication Date: 2026.03.17 NOGRA PHARMA LTD

AI summary

The present invention is generally directed towards compounds capable of binding the aryl hydrocarbon receptor and modulating its activity, methods of treating inflammatory conditions such as Crohn's disease using such compounds, and pharmaceutical compositions comprising such compounds. Also provided are methods of increasing levels of IL-22 in a subject and/or decreasing levels of IFN-7 in a subject.