RORγ Modulators Targeting TH17 Immune Response

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Solution Overview

Problem

Current treatments for autoimmune and inflammatory diseases, particularly those mediated by RORγ, lack effective modulators to target TH17 cells and non-TH17 IL-17 producing cells, leading to inadequate therapeutic outcomes.

Innovation Solution

Development of novel compounds according to Formula I, which are modulators of RORγ, specifically designed to inhibit RORγ activity, thereby addressing the underlying immune response in autoimmune and inflammatory diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for autoimmune and inflammatory diseases are used, then existing therapeutic approaches are maintained, but effective modulation of RORγ activity to target TH17 cells and non-TH17 IL-17 producing cells is lacking

Engineering Contradiction:

Improvetherapeutic outcomeVSAvoidability to target RORγ-mediated immune response

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by developing novel chemical compounds with specific molecular structures (Formula I) that modify the pharmacological parameters of RORγ modulation. These compounds represent a change in chemical parameters to achieve effective RORγ inhibition, thereby improving therapeutic outcomes for autoimmune and inflammatory diseases while specifically targeting TH17 cells and non-TH17 IL-17 producing cells

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If novel compounds according to Formula I are developed to modulate RORγ, then specific targeting of TH17 cells and non-TH17 IL-17 producing cells is achieved, but the complexity of the compound structure increases

Engineering Contradiction:

Improvespecificity to RORγ and IL-17 producing cellsVSAvoidmolecular structure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the molecular structure into distinct functional segments represented by variables (R1 through R6, A1 through A6) in Formula I. This segmentation allows for systematic optimization of specific RORγ targeting while managing structural complexity through modular design, enabling specific targeting of TH17 cells and non-TH17 IL-17 producing cells

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS10556866B2ROR gamma (RORγ) modulators

Publication Date: 2020.02.11 LEAD PHARMA HLDG

AI summary

Novel compounds according to Formula Ior a pharmaceutically acceptable salt thereof wherein: A11-A14 are N or CR11, CR12, CR13, CR14, respectively, with the proviso that no more than two of the four positions A can be simultaneously N; R1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino; R5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, (3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl; the sulfonyl group with R1 is represented by one of R7, R8 or R9; R15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl; and R16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl. The compounds can be used as inhibitors of RORγ and are useful for the treatment of RORγ mediated diseases.