Selenium Compounds Inhibit IMPase for Bipolar Disorder

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Solution Overview

Problem

Current treatments for bipolar disorder, such as lithium, suffer from toxicity and side effects due to non-specificity and poor bio-permeability, while existing compounds lacking IMPase inhibition activity fail to provide effective alternatives.

Innovation Solution

Development of compounds like ebselen and 2-phenyl-1,2-benzisothiazol-3(2H)-one, which are specific IMPase inhibitors, capable of crossing the blood-brain barrier and offering reduced toxicity, for use in treating bipolar disorder.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If lithium is used to treat bipolar disorder, then therapeutic effectiveness is improved, but toxicity and side effects increase

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidtoxicity and side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical structure parameter from lithium salt to organic compound (ebselen and derivatives), maintaining therapeutic effectiveness through IMPase inhibition while altering toxicity parameters to reduce harmful effects

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts the essential therapeutic mechanism (IMPase inhibition) from lithium and isolates it in specific organic compounds, separating the desired therapeutic effect from the unwanted toxicity associated with lithium

Inventive Principle:
Principle #2Taking out (Extraction)

2Reliability

If lithium is used to treat bipolar disorder, then mood stabilization is achieved, but bio-permeability limitations reduce efficacy

Engineering Contradiction:
Improvemood stabilizationVSAvoidbio-permeability
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the physical-chemical parameters of the treatment agent from inorganic lithium salt to organic compounds with optimized molecular properties, improving blood-brain barrier penetration while maintaining therapeutic action

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If existing IMPase inhibitor compounds are developed, then specificity is improved, but poor bio-permeability and inhibition reduce effectiveness

Engineering Contradiction:
Improveenzyme specificityVSAvoidinhibition effectiveness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent combines the specific IMPase inhibition mechanism with organic molecular structures that provide both specificity and bio-permeability, creating a composite therapeutic agent that addresses multiple requirements simultaneously

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent optimizes molecular parameters of the inhibitor compounds, including lipophilicity and molecular size, to achieve both high enzyme specificity and adequate bio-permeability for effective brain penetration

Inventive Principle:
Principle #35Parameter changes

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

These compounds effectively inhibit IMPase, providing a safer and more specific treatment option for bipolar disorder, with ebselen demonstrating bio-availability and low toxicity, potentially replacing lithium in clinical trials.

Implementation Method 1

the ability to inhibit the enzyme inositol monophosphatase (IMPase) is a key factor in the control of bipolar disorder. IMPase catalyses the hydrolysis of inositol monophosphate (IP 1) to inositol

Methodology Applied
Scientific EffectEnzyme inhibition: Enzyme

Implementation Method 2

capable of crossing the blood-brain barrier and offering reduced toxicity

Methodology Applied
Scientific EffectBlood-brain barrier permeation: Permeation

Data Source

PatentEP2673048B1Treatment of bipolar disorder
Publication Date: 2016.01.13 OXFORD UNIVERSITY INNOVATION LTD
  • EP2673048B1 patent drawingFigure 1
  • EP2673048B1 patent drawingFigure 2~3
  • EP2673048B1 patent drawingFigure 4~5

AI summary

The invention relates to sulphur- and/or selenium-containing compounds that can inhibit the enzyme inositol monophosphatase (IMPase), and which can be used in treating conditions that are treatable through inhibition of this enzyme, such as bipolar disorder, the compounds having a structure of Formula I, or is a pharmaceutically acceptable salt thereof; Formula I; in which: E is S or Se and each of phenyl rings A and B is optionally substituted with one or more substituents, in which each substituent is selected independently from: (1) a halogen, which is preferably selected from F, Cl and Br; (2) C1-C4 alkyl, such as C1-C2 alkyl or C1 alkyl, optionally substituted with one or more halogen atoms, each of which is preferably selected from F, Cl and Br; and (3) C1-C4 alkoxy, such as C1-C2 alkoxy or C1 alkoxy; optionally substituted with one or more halogen atoms, each of which is preferably selected from F, Cl and Br.