Indoline Derivatives for Oxidative Stress and Cytokine Control
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Solution Overview
Problem
Current treatments for chronic inflammatory and neurodegenerative disorders, such as rheumatoid arthritis, Alzheimer's disease, and diabetic nephropathy, often lead to adverse effects and fail to address the underlying oxidative stress and pro-inflammatory cytokine release effectively, while mTOR inhibitors for tuberous sclerosis have limited efficacy and side effects.
Innovation Solution
Indoline derivatives and their salts, which act as immunomodulators, reduce oxidative stress and pro-inflammatory cytokine release without blocking their receptors, and can modulate mTOR activity to treat a wide range of inflammatory and neurodegenerative conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for chronic inflammatory and neurodegenerative disorders are used, then disease symptoms are addressed, but adverse effects occur and underlying oxidative stress and pro-inflammatory cytokine release are not effectively reduced
Solution Approach 1:
The patent introduces indoline derivatives as intermediary compounds that act upstream in the inflammatory pathway by inhibiting NLRP3 inflammasome activation and reducing oxidative stress. These compounds serve as mediators that prevent the formation of harmful pro-inflammatory cytokines (IL-1β, IL-18) without directly blocking their receptors, thereby treating inflammatory conditions while avoiding the adverse effects associated with conventional treatments that directly inhibit cytokine receptors or use immunosuppressants.
2Object-affected harmful factors
If TNF blockers are used to treat inflammatory conditions, then inflammation is reduced, but the risk of serious infections and malignancies increases
Solution Approach 1:
The patent converts the harmful overactivation of the NLRP3 inflammasome pathway into a beneficial therapeutic target. By specifically inhibiting NLRP3 activation and reducing oxidative stress upstream, the indoline derivatives selectively reduce harmful pro-inflammatory cytokine production while preserving the body's natural immune defenses against infections and malignancies, unlike broad-spectrum TNF blockers that suppress overall immune function.
3Reliability
If mTOR inhibitors are used for tuberous sclerosis, then some efficacy is achieved, but limited effectiveness and side effects remain
Solution Approach 1:
The patent applies local quality by targeting the specific NLRP3 inflammasome pathway and oxidative stress mechanisms that are dysregulated in tuberous sclerosis and related conditions. The indoline derivatives act locally on the inflammasome activation cascade and reactive oxygen species production, providing targeted therapeutic effect without the broad-spectrum side effects of mTOR inhibitors that affect multiple cellular processes.
Data Source
AI summary
The present invention is directed to indoline derivatives and salts thereof, compositions comprising them and uses thereof for the treatment of diseases and disorders associated with at least one of oxidative stress, an immune response, release of NO and release of pro-inflammatory cytokine.