Pyridine-2-amide CB2 Agonists with Selective Binding

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Solution Overview

Problem

Current treatments for conditions such as pain, atherosclerosis, and inflammatory diseases lack effective therapies, particularly in targeting Cannabinoid Receptor 2 (CB2) for therapeutic benefits without significant CB1 receptor activity.

Innovation Solution

Development of a compound of formula (I) that selectively binds to and modulates the CB2 receptor, reducing CB1 receptor activity, to treat various diseases including pain, atherosclerosis, and inflammatory conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a compound is designed to target CB2 receptors for therapeutic benefit, then therapeutic efficacy for pain and inflammatory conditions is improved, but selectivity against CB1 receptors must be maintained to avoid unwanted side effects

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidCB1 receptor activity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by introducing specific substituent patterns at defined positions on the pyridine ring structure. Different substituents (R1-R6) are placed at specific locations to optimize CB2 binding affinity while maintaining CB1 selectivity, allowing the molecule to have different properties at different spatial locations

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by systematically varying chemical parameters such as substituent types, chain lengths, and functional groups on the pyridine core structure. This allows optimization of the compound's binding characteristics to achieve high CB2 affinity with minimal CB1 activity

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If existing treatments are used for pain and inflammatory conditions, then broad coverage is achieved, but effectiveness is insufficient due to lack of targeted CB2 receptor modulation

Engineering Contradiction:

Improvebroad coverageVSAvoideffectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent achieves universality by designing a pyridine-2-amide core structure with multiple possible substituent variations that can address different inflammatory conditions and pain types. The basic scaffold maintains broad applicability while specific substitutions tailor the activity for different indications

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Ease of manufacture

If compound structure is simplified for ease of manufacture, then production cost is reduced, but selectivity and affinity for CB2 receptors may be compromised

Engineering Contradiction:

Improveproduction costVSAvoidCB2 receptor selectivity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent applies segmentation by dividing the molecule into distinct functional modules: a core pyridine-2-amide structure and variable substituent groups. This modular approach allows independent optimization of each segment, where the core provides essential binding features and substituents fine-tune selectivity and affinity

Inventive Principle:

Principle #1Segmentation

Data Source

PatentEP2928868B1Pyridine-2-amides useful as CB2 agonists

Publication Date: 2017.08.09 F HOFFMANN LA ROCHE & CO AG

AI summary

The invention relates to CB2 agonists of formula (I) wherein R1 to R4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.