Heterocyclic Sulfone RORγ Modulators for Autoimmune Disease

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Solution Overview

Problem

Current therapeutic agents for inflammatory and autoimmune diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease, have limitations in effectively targeting IL-17 and RORγ pathways, leading to unmet medical needs in managing these conditions.

Innovation Solution

Development of compounds, specifically those of Formula (I), which act as modulators of RORγ, capable of modulating RORγ activity to treat inflammatory, autoimmune, allergic, metabolic, and cancer-related diseases by inhibiting or reducing RORγ receptor activities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapeutic agents are used to treat inflammatory and autoimmune diseases, then treatment is provided, but the effectiveness in targeting IL-17 and RORγ pathways is insufficient

Engineering Contradiction:

Improveeffectiveness in targeting IL-17 and RORγ pathwaysVSAvoidability to modulate RORγ activity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical structure of RORγ modulators by changing parameters such as introducing a sulfone group at specific positions in the molecule, adjusting substituent types and positions, and modifying physical-chemical properties to enhance binding affinity and selectivity for RORγ receptors, thereby improving therapeutic effectiveness

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures by combining multiple functional moieties within a single RORγ modulator compound, integrating heterocyclic rings, sulfone groups, and various substituents to achieve multi-point interaction with the receptor and enhanced biological activity

Inventive Principle:

Principle #40Composite materials

2Reliability

If current therapeutic agents are used, then treatment is provided, but there remains unmet medical need in managing inflammatory and autoimmune conditions

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidlimitations in managing diseases

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and isolates the specific RORγ modulation function from non-specific immunosuppression, creating compounds that selectively target RORγ receptors to produce IL-17-dependent effects, thereby removing the harmful non-specific side effects of conventional agents while preserving therapeutic benefits

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the potentially harmful dysregulated IL-17 production into a beneficial controlled response by using RORγ modulators that can selectively enhance or suppress IL-17 signaling pathways depending on the disease state, transforming the double-edged sword of IL-17 into a controllable therapeutic mechanism

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP3526218B1Heterocyclic sulfones as ROR gamma modulators

Publication Date: 2021.04.21 BRISTOL MYERS SQUIBB CO

AI summary

There are described 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 Gamma 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 Gamma activity, for example, autoimmune and/or inflammatory disorders.