Sulfanone Derivative Nrf2 Activation Metabolic Stability
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Solution Overview
Problem
Existing Nrf2 activators, such as sulforaphane, suffer from issues like cytotoxicity, low blood-brain barrier permeability, and short duration of action, limiting their effectiveness in activating Nrf2 and providing antioxidant and anti-inflammatory benefits.
Innovation Solution
A novel sulfanone derivative or its pharmaceutically acceptable salt, specifically designed to activate Nrf2, with improved solubility, metabolic stability, and enhanced anti-inflammatory and antioxidant effects, is developed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If sulforaphane is administered at a high concentration to maintain constant Nrf2 activation, then the duration of action is improved, but cytotoxicity increases
Solution Approach 1:
The patent modifies the chemical structure of sulforaphane by replacing the nitrile group with an isothiocyanate group and introducing aromatic substituents, creating compound (1) with improved metabolic stability and prolonged Nrf2 activation duration without requiring high concentrations that cause cytotoxicity
Solution Approach 2:
The patent combines the sulforaphane core structure with aromatic rings and electron-withdrawing groups to create a composite molecular structure that enhances both the duration of Nrf2 activation and metabolic stability while reducing cytotoxic effects
2Reliability
If sulforaphane is used to activate Nrf2, then antioxidant and anti-inflammatory effects are improved, but blood-brain barrier permeability remains low
Solution Approach 1:
The patent introduces aromatic rings and electron-withdrawing groups to the sulforaphane structure, modifying lipophilicity and molecular properties to enhance blood-brain barrier permeability while preserving the compound's ability to activate Nrf2 and provide antioxidant and anti-inflammatory effects
3Reliability
If existing Nrf2 activators are used, then Nrf2 activation effect is achieved, but metabolic stability is poor leading to short duration of action
Solution Approach 1:
The patent replaces the metabolically labile nitrile group of sulforaphane with a more stable isothiocyanate group and introduces aromatic substituents, creating compound (1) with enhanced metabolic stability that maintains prolonged Nrf2 activation without rapid degradation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The sulfanone derivative effectively activates Nrf2, improves motor performance and cognitive ability, and demonstrates potential in preventing or treating diseases induced by decreased Nrf2 activity, such as liver and kidney diseases, neurodegenerative disorders, and others.
Implementation Method 1
Such electrophilic compounds or reactive oxygen species react with cysteine residue of Keap1 to oxidize or covalently bond the thiol group, thereby causing a change in the structure of the KEAP1
Data Source
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AI summary
The present invention relates to a sulfanone derivative or a pharmaceutically acceptable salt thereof, and a composition containing the derivative as an active ingredient for the prevention or treatment of cancer, and the sulfanone derivative of the present invention or a pharmaceutically acceptable salt thereof exhibits an excellent effect on Nrf2 activation and a high solubility and pharmaco-metabolic stability, has anti-inflammatory and antioxidant effects, and improves motor performance and cognitive ability, and thus can be used for the prevention or treatment of diseases induced by a decrease in the Nrf2 activity, preferably liver diseases, kidney diseases, lung diseases, neurodegenerative diseases, mitochondrial myopathy, Friedreich's ataxia, corneal endothelial cell loss, psoriasis, and the like.