Bis Aryl Analog Nrf2 Regulators for Oxidative Stress
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for various diseases such as COPD, asthma, and kidney diseases lack effective Nrf2 regulators, which are crucial for managing oxidative stress and inflammation, leading to inadequate protection and repair of lung and kidney tissues.
Innovation Solution
Development of bis aryl analogs that act as Nrf2 regulators, administered as pharmaceutical compositions to modulate Nrf2 activity, thereby treating and preventing conditions associated with Nrf2 imbalance across multiple disease types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for diseases such as COPD and asthma, then existing therapy protocols are maintained, but Nrf2 activity remains insufficient leading to inadequate cytoprotection and tissue repair
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of Nrf2 regulator compounds. The bis-aryl analogs (Formula I) feature specific structural parameters including aryl groups at positions 1 and 2, various substituent options (R1-R6), and structural variations (Formula Ia and Ib) that optimize Nrf2 activation potency and efficacy to overcome insufficient Nrf2 activity in current treatments
Solution Approach 2:
The patent employs composite materials by creating bis-aryl analog compounds that combine multiple aromatic rings and functional groups into a single molecular structure. These composite molecular structures (Formula I) integrate electron-donating and electron-withdrawing groups, various aryl substitutions, and linker moieties to achieve enhanced Nrf2 regulatory activity compared to simpler compounds
2Object-generated harmful factors
If Nrf2 activity is not restored in COPD patients, then disease progression continues with cell apoptosis and inflammation, but introducing new Nrf2 regulator compounds increases treatment complexity
Solution Approach 1:
The patent applies universality by designing Nrf2 regulator compounds (Formula I) that address multiple pathological mechanisms simultaneously. These compounds provide cytoprotection, reduce inflammation, prevent apoptosis, and promote tissue repair through Nrf2 activation, making a single agent that tackles several harmful effects rather than requiring multiple separate treatments
Solution Approach 2:
The patent employs self-service by activating the body's endogenous Nrf2 pathway, which then autonomously orchestrates multiple protective responses. Once Nrf2 is activated by these compounds, it automatically upregulates antioxidant enzymes, anti-inflammatory mediators, and cytoprotective proteins, allowing the body's own defense systems to handle the pathology without requiring complex external intervention
3Reliability
If macrophage function is not restored in COPD patients, then bacterial phagocytosis and clearance remain impaired, but additional targeted therapies increase treatment complexity
Solution Approach 1:
The patent applies universality by demonstrating that Nrf2 activation with these compounds simultaneously restores multiple macrophage functions. A single compound treatment rejuvenates phagocytic activity, bacterial clearance capability, and anti-inflammatory responses in macrophages, providing multi-functional restoration rather than requiring separate therapies for each defect
Data Source
AI summary
The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators.