Chroman Derivatives for COPD Inhalation Therapy

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Solution Overview

Problem

Current treatments for chronic obstructive airway diseases such as COPD, asthma, and bronchiectasis often require multiple medications and have limitations in providing both bronchodilating and anti-inflammatory effects without causing desensitization, and existing drugs are not effective in addressing chronic inflammation and airway obstruction effectively.

Innovation Solution

Development of compounds with a chroman skeleton, specifically formula (I), (II), and (III), which are derived from trolox and have bronchodilating and anti-inflammatory properties, suitable for inhalation, and can be administered through a nebulizer to target chronic obstructive airway diseases, maintaining activity over long-term use without desensitization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple medications are used to treat chronic obstructive airway diseases, then the therapeutic coverage is improved, but the treatment complexity increases

Engineering Contradiction:
Improvetherapeutic coverageVSAvoidtreatment complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent combines bronchodilating and anti-inflammatory effects into a single chroman derivative compound, eliminating the need for multiple medications while maintaining comprehensive therapeutic coverage for chronic obstructive airway diseases

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If existing drugs are used to address chronic inflammation and airway obstruction, then some symptomatic relief is achieved, but desensitization occurs over time

Engineering Contradiction:
Improveinitial efficacyVSAvoidlong-term effectiveness
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the chemical structure by introducing specific substituents at the 6-position of the chroman ring, creating derivatives with optimized pharmacological properties that maintain effectiveness over long-term use without causing desensitization

Inventive Principle:
Principle #35Parameter changes

3Reliability

If inhaled medications are administered to target lung diseases, then localized treatment efficacy is improved, but absorption efficiency must be optimized

Engineering Contradiction:
Improvelocalized treatment efficacyVSAvoidabsorption efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent optimizes the lipophilicity and molecular weight of chroman derivatives to enhance their absorption through inhalation, ensuring efficient delivery to lung tissue while maintaining appropriate pharmacokinetic properties for localized action

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3157518B16-hydroxy-2,5,7,8-tetramethylchroman-compounds for the treatment of chronic obstructive airway diseases
Publication Date: 2020.01.15 SULFATEQ BV
  • EP3157518B1 patent drawingFigure 1
  • EP3157518B1 patent drawingFigure 2
  • EP3157518B1 patent drawingFigure 3

AI summary

The present invention relates to compounds for the treatment of chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD) or asthma or bronchiectasis. The present invention further relates to drug delivery devices suitable to be used in the treatment of chronic obstructive airway diseases such as a nebulizer comprising the present compounds. Specifically, the present invention relates to (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(piperazin-1-yl)methanone or N,6-dihydroxy-2,5,7,8-tetramethylchroman-2-carboxamide or a pharmaceutically acceptable salt or base thereof for use in the treatment of chronic obstructive airway diseases, preferably chronic obstructive pulmonary disease (COPD) or asthma or bronchiectasis, more preferably chronic obstructive pulmonary disease (COPD).