Phosphate ROR Modulators for Improved Pulmonary Absorption

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Solution Overview

Problem

There is a need for new ROR modulators with improved pharmacokinetic properties to provide more efficient treatment for respiratory diseases such as asthma and COPD.

Innovation Solution

Development of phosphate derivatives of ROR modulators with enhanced solubility, stability, and metabolization in the organism, facilitating absorption in the lungs, particularly in the form of compounds with specific structural formulas and stereoisomers, along with pharmaceutical compositions for administration via nasal inhalation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If new ROR modulators are developed for treating respiratory diseases, then therapeutic efficacy is improved, but pharmacokinetic properties (solubility, stability, absorption) are insufficient

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidpharmacokinetic properties
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of ROR modulators through phosphate derivative formation. This chemical modification transforms the original compounds into phosphate esters, which fundamentally changes their physicochemical parameters including solubility, stability, and metabolic properties, thereby resolving the pharmacokinetic deficiencies while maintaining therapeutic efficacy

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures by combining the ROR modulator core structure with phosphate groups. This composite approach integrates the therapeutic activity of the original modulator with the enhanced pharmacokinetic properties of phosphate derivatives, achieving both improved efficacy and better absorption/stability characteristics

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If phosphate derivatives are developed to improve solubility and stability, then absorption in lungs is enhanced, but molecular complexity increases

Engineering Contradiction:
Improveabsorption in lungsVSAvoidmolecular complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The phosphate derivative modification changes key physicochemical parameters of the ROR modulators, specifically enhancing water solubility and metabolic stability. These parameter changes directly improve pulmonary absorption characteristics without requiring complex delivery systems or formulation approaches

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP4077342B1Phosphate derivatives of rorgamma modulators and uses thereof
Publication Date: 2025.12.10 GENFIT SA
  • EP4077342B1 patent drawingFigure 1
  • EP4077342B1 patent drawingFigure 2~3A
  • EP4077342B1 patent drawingFigure 3B~3C

AI summary

The present invention relates to phosphate derivatives of formula (I), and their therapeutic uses, preferably for treating a respiratory disease. The present invention further relates to pharmaceutical compositions and devices comprising such compounds.