Formula I Compounds Inhibiting eEF2K Activity

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Solution Overview

Problem

Current eEF2K inhibitors are not suitable for use as pharmaceutical agents to treat various diseases, including cancer and radiation-induced injuries, as they fail to effectively inhibit EF2 phosphorylation.

Innovation Solution

Development of specific compounds, such as those of formula I, which inhibit eukaryotic elongation factor 2 kinase (eEF2K) activity, are used in pharmaceutical compositions to limit EF2 phosphorylation, thereby treating conditions like cancer, radiation injuries, and neurodegenerative diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If known eEF2K inhibitors are used, then some inhibition activity is achieved, but they fail to effectively inhibit EF2 phosphorylation and are not suitable for pharmaceutical use

Engineering Contradiction:

Improveinhibition effectivenessVSAvoidpharmaceutical suitability

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent modifies chemical parameters of eEF2K inhibitors by changing molecular structure (introducing specific substituents R1-R8 at defined positions), optimizing the balance between inhibition potency and pharmaceutical properties such as solubility, stability, and bioavailability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures combining multiple functional groups (amino, carbonyl, heterocyclic rings) into a single pharmaceutical compound that simultaneously achieves effective eEF2K inhibition and desirable drug-like properties

Inventive Principle:

Principle #40Composite materials

2Object-affected harmful factors

If EF2 phosphorylation is inhibited to treat cancer, then tumor growth is suppressed, but normal cells may also be affected

Engineering Contradiction:

Improvecancer treatment efficacyVSAvoidside effects on normal cells

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent achieves selective inhibition by designing compounds that specifically target eEF2K in cancer cells through localized molecular interactions, allowing differential effects based on cellular context and disease state

Inventive Principle:

Principle #3Local quality

3Object-affected harmful factors

If eEF2K inhibition is used to protect from radiation injury, then radiation-induced apoptosis is limited, but the mechanism of selective protection remains unclear

Engineering Contradiction:

Improveradiation protectionVSAvoidmechanism complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent introduces eEF2K inhibition as an intermediary mechanism that mediates protection against radiation injury by preventing EF2 phosphorylation, thereby blocking the downstream apoptotic pathway without directly interacting with radiation

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10106552B2Compounds inhibiting eukaryotic elongation factor 2 kinase activity

Publication Date: 2018.10.23 LONGEVICA PHARMA

AI summary

Eukaryotic elongation factor 2 kinase inhibitors of the formulawhere R1, R2, R3a, R3b, R4a, R4b, R5a, R5b, R6a, R6b, R7 and x are as defined in the specification, pharmaceutical compositions and formulations including compounds of the foregoing formula, and methods of preventing, ameliorating or treating indications, conditions, disorders or syndromes associated with elongation factor 2 phosphorylation.