Tri-substituted Aryl Compounds Modulating PI3K-AKT-mTOR Pathway

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for compounds that can effectively modulate the PI3K-AKT-MTOR pathway to treat neurodegenerative disorders and other diseases associated with autophagy regulation, as existing therapies are inadequate in addressing mis-regulation of this pathway.

Innovation Solution

Tri-substituted aryl and heteroaryl compounds that inhibit the PI3K-AKT-MTOR pathway by inhibiting the phosphorylation of AKT and mTOR, thereby increasing markers of autophagy and promoting cellular clearance of toxic protein aggregates, are developed.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapies are used to treat neurodegenerative disorders, then treatment is provided, but they are inadequate in addressing mis-regulation of the PI3K-AKT-MTOR pathway

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidability to address pathway mis-regulation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops novel tri-substituted aryl and heteroaryl compounds with specific chemical structures designed to modulate the PI3K-AKT-MTOR pathway. By changing the chemical parameters and molecular structure of the therapeutic agents, the invention creates compounds that specifically target and correct the pathway mis-regulation that existing therapies fail to address, thereby improving both reliability and adaptability of treatment

Inventive Principle:

Principle #35Parameter changes

2Productivity

If the PI3K-AKT-MTOR pathway is inhibited to upregulate autophagy, then cellular clearance of toxic protein aggregates increases, but the pathway regulating cell survival and energetics is affected

Engineering Contradiction:

Improvecellular clearance of toxic protein aggregatesVSAvoidcell survival and energetics regulation

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent employs compounds with specific local chemical structures (tri-substituted aryl and heteroaryl groups) that are designed to interact with specific components of the PI3K-AKT-MTOR pathway. This localized molecular design allows selective modulation of the pathway at specific points, enabling enhanced autophagy and protein aggregate clearance while minimizing disruption to the overall pathway functions regarding cell survival and energetics

Inventive Principle:

Principle #3Local quality

3Object-affected harmful factors

If PI3K inhibition is used to reduce oxidative stress, then ROS and oxidative stress signaling are reduced, but the central role of PI3K in ROS/RNS formation regulation is disrupted

Engineering Contradiction:

Improveoxidative stress and ROS formationVSAvoidcellular oxidation-reduction homeostasis

Core Design Contradiction:

Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent introduces tri-substituted aryl and heteroaryl compounds as intermediary substances that mediate the interaction between therapeutic intervention and the PI3K-AKT-MTOR pathway. These intermediary compounds selectively inhibit PI3K to reduce harmful oxidative stress and ROS formation while maintaining the pathway's essential regulatory functions, thus reducing harmful factors without completely disrupting cellular homeostasis

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240327396A1TRI-substituted ARYL and heteroaryl derivatives as modulators of PI3-kinase and autophagy pathways

Publication Date: 2024.10.03 GLOBAL CANCER TECHNOLOGY INC

AI summary

The present disclosure relates to tri-substituted aryl and heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for modulating autophagy or preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods of treating diseases that are associated with autophagy or the PI3K-AKT-MTOR pathway.