P2X7 Modulator Compounds for Neuroinflammation

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Solution Overview

Problem

Current therapies lack effective modulators for the P2X7 receptor, which is implicated in various inflammatory and neurological disorders, including pain, mood disorders, and neuroinflammation, highlighting the need for compounds that can specifically target and modulate P2X7 receptor activity.

Innovation Solution

Development of compounds of Formula (I) and their pharmaceutically acceptable salts, which are designed to modulate P2X7 receptor activity, including enantiomers, diastereomers, and isotopic variations, for use in pharmaceutical compositions to treat diseases mediated by P2X7 receptor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies are used, then treatment of inflammatory and neurological disorders is provided, but effective modulators for P2X7 receptor are lacking

Engineering Contradiction:

Improveeffectiveness of P2X7 receptor modulationVSAvoidavailability of P2X7 receptor modulators

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the therapeutic approach by developing distinct chemical series (e.g., compounds of Formula I with various R1, R2, R3 substitutions) that can be selectively optimized for different P2X7 receptor modulation needs, allowing targeted treatment of specific inflammatory and neurological conditions

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent systematically varies chemical parameters including substituent groups (halogens, alkyls, aryls at positions R1-R6), stereochemistry (enantiomers and diastereomers), and molecular weight to optimize P2X7 receptor binding affinity and selectivity, thereby improving modulation effectiveness

Inventive Principle:

Principle #35Parameter changes

2Reliability

If P2X7 receptor is targeted for therapeutic benefit, then treatment of pain and neuroinflammation is improved, but understanding of receptor pharmacology is limited

Engineering Contradiction:

Improvetherapeutic benefit for pain and neuroinflammationVSAvoidpharmacological understanding of P2X7 receptor

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent incorporates structure-activity relationship (SAR) analysis that provides feedback on how specific molecular features correlate with P2X7 receptor binding and functional outcomes, building pharmacological knowledge through iterative optimization of compound series

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent performs preliminary pharmacological characterization of novel P2X7 modulators including in vitro binding assays and in vivo efficacy studies in pain and neuroinflammation models, establishing a foundation of receptor knowledge before clinical development

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentEP3191492B1P2x7 modulators

Publication Date: 2019.01.09 JANSSEN PHARMA NV

AI summary

The present invention is directed to compounds of Formula (I), which includes enantiomer and diasteromers thereof. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) as P2X7 modulators are also within the scope of the invention.