Indole Amine Composition for NASH Treatment via Mitochondrial Protection
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Solution Overview
Problem
Current treatments for non-alcoholic steatohepatitis (NASH) are inadequate, with existing medications like pioglitazone showing limited effectiveness and significant side effects, and there is a lack of clinical evidence for effective prevention or treatment options.
Innovation Solution
A pharmaceutical composition containing (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine or its pharmaceutically acceptable salt, which inhibits liver fat accumulation, inflammation, and fibrosis by targeting oxidative stress and inflammatory cytokines, thereby addressing the pathological mechanisms of NASH.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pioglitazone is used as an insulin resistance improving agent for NASH treatment, then insulin resistance is improved, but side effects such as fracture risk, weight gain, and heart failure deterioration occur
Solution Approach 1:
The patent extracts and applies a specific compound (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine that targets mitochondrial necrosis specifically, separating the therapeutic effect from the harmful side effects associated with broader-acting drugs like pioglitazone
Solution Approach 2:
The invention changes the therapeutic parameter from general insulin resistance improvement to specific mitochondrial necrosis inhibition, thereby achieving NASH treatment effectiveness while avoiding the side effects associated with insulin sensitizers
2Reliability
If existing medicaments are used for NASH treatment, then some metabolic syndrome symptoms are improved, but clinical evidence for effective NASH treatment is lacking
Solution Approach 1:
The patent performs preliminary action by conducting comprehensive animal model studies and mechanistic research on mitochondrial necrosis inhibition before clinical application, establishing a solid evidence base that addresses the lack of clinical evidence for existing NASH treatments
3Reliability
If (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine is used for NASH treatment, then liver fat accumulation, inflammation, and fibrosis are reduced, but the mechanism of action is complex involving multiple pathways
Solution Approach 1:
The patent segments the complex mechanism into distinct components: mitochondrial necrosis inhibition as the primary action, with downstream effects on oxidative stress reduction, inflammation suppression, and fibrosis prevention, allowing for targeted therapeutic intervention
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 composition effectively reduces liver fat, inflammation, and fibrosis, demonstrating potential as a viable treatment for NASH by inhibiting fatty liver disease progression and improving mitochondrial function.
Implementation Method 1
(tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine is a cellular necrosis inhibitor which is specific for mitochondria, and shows effects on inhibiting cell death by toxins or stress
Implementation Method 2
shows effects on inhibiting cell death by toxins or stress, increasing viability of cells, and antioxidation and anti-inflammation at the same time
Implementation Method 3
shows effects on inhibiting cell death by toxins or stress, increasing viability of cells, and antioxidation and anti-inflammation at the same time
Data Source
Figure 1A~1C
Figure 2A~2C
Figure 3A~3C
AI summary
The present invention relates to a pharmaceutical composition for preventing or treating fatty liver diseases, containing (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine or a pharmaceutically acceptable salt thereof as active ingredients. (Tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine or a pharmaceutically acceptable salt thereof, according to the present invention, can effectively inhibit fatty liver, hepatitis and hepatic fibrosis and can be useful for preventing or treating NAFLD, and in particular, NASH.