Substituted Thiazole P2X7 Antagonists Brain Delivery

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Solution Overview

Problem

There is an unmet need for compounds that can efficiently antagonize the P2X7 receptor and be delivered to various target organs, including the brain, to treat P2X7-mediated pathologies.

Innovation Solution

Development of novel substituted thiazole and oxazole compounds with P2X7 receptor antagonistic properties, specifically formulated to target and inhibit the P2X7 receptor in different organs, including the brain, through pharmaceutical compositions and chemical processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing P2X7 antagonists are used, then some level of receptor antagonism is achieved, but the compounds lack efficient delivery to target organs including the brain

Engineering Contradiction:

ImproveP2X7 receptor antagonismVSAvoidDelivery to target organs

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent modifies the molecular structure of P2X7 antagonists by introducing specific substituents at defined positions (R1-R6, R7) to create compounds with enhanced properties for delivery to specific target organs including the brain, while maintaining P2X7 receptor antagonistic activity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent systematically varies chemical parameters (substituents at positions R1-R6, R7, heteroatom Y) to optimize the pharmacokinetic properties and delivery characteristics of the compounds to target organs while preserving receptor binding affinity

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If P2X7 antagonists are developed for brain delivery, then neurological disorders can be treated, but the compound structure becomes more complex

Engineering Contradiction:

ImproveTreatment of neurological disordersVSAvoidCompound structure

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent creates a series of compounds with a common core structure that can be delivered to the brain and other target organs, providing a universal platform for treating multiple neurological disorders including Alzheimer's, Parkinson's, epilepsy, and depression through systematic variation of substituents

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If new substituted thiazole and oxazole compounds are synthesized, then P2X7 antagonistic activity is improved, but the manufacturing process becomes more complex

Engineering Contradiction:

ImproveP2X7 antagonistic activityVSAvoidSynthesis process

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent divides the synthesis process into modular steps where core compounds are first synthesized, then systematically substituted at specific positions (R1-R6, R7) using standardized coupling reactions, enabling efficient manufacturing of multiple analogs through a segmented approach

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS10167281B2Substituted thiazole or oxazole P2X7 receptor antagonists

Publication Date: 2019.01.01 BREYE THERAPEUTICS APS

AI summary

The present invention refers to novel substituted thiazole and oxazole compounds of formula (I) having P2X7 receptor (P2X7) antagonistic properties:The compounds are useful in the treatment or prophylaxis of diseases associated with P2X7 receptor activity in animals, in particular humans.