Spirocyclic Amide Derivatives Dual Muscarinic Beta2 Agonists

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Solution Overview

Problem

Current treatments for pulmonary disorders like COPD and asthma often require co-administration of muscarinic-receptor antagonists and β-adrenoceptor agonists, which can be cumbersome and may not offer optimal efficacy and side-effect profiles, suggesting a need for a single molecule with dual activity.

Innovation Solution

Development of spirocyclic amide derivatives that act as both muscarinic and β2-receptor agonists, potentially providing improved efficacy, side-effect profiles, and patient compliance through a single agent.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If co-administration of muscarinic-receptor antagonists and β-adrenoceptor agonists is used, then efficacy is improved, but treatment complexity and patient compliance deteriorate

Engineering Contradiction:
ImproveefficacyVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent combines two separate therapeutic agents (muscarinic-receptor antagonist and β2-adrenoceptor agonist) into a single dual-action molecule. This merging approach maintains the therapeutic benefits of both agents while simplifying the treatment regimen to a single medication, thereby improving patient compliance without compromising efficacy

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a single molecule that performs multiple functions by acting on both muscarinic receptors and β2-adrenoceptors. This multi-functional compound addresses the limitations of single-agent therapies while avoiding the complexity of co-administration, achieving both improved compliance and maintained efficacy

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If co-administration of two separate compounds is used, then therapeutic coverage is improved, but formulation complexity deteriorates

Engineering Contradiction:
Improvetherapeutic coverageVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges two separate compounds into a single dual-action molecule, thereby simplifying the formulation from two separate medications to one. This approach maintains comprehensive therapeutic coverage while reducing formulation complexity, storage requirements, and dosing instructions

Inventive Principle:
Principle #5Merging (Combining)

3Ease of operation

If single molecule with dual activity is used, then patient compliance is improved, but molecular complexity deteriorates

Engineering Contradiction:
Improvepatient complianceVSAvoidmolecular complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The invention designs a single molecule with dual pharmacological activity that can interact with both muscarinic receptors and β2-adrenoceptors. While the molecular structure is more complex than single-agent compounds, this complexity is justified by the significant improvement in patient compliance and the elimination of co-administration requirements

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP2242759B1compounds
Publication Date: 2012.09.12 PULMAGEN THERAPEUTICS (SYNERGY) LIMITED
  • EP2242759B1 patent drawingFigure 1~2
  • EP2242759B1 patent drawingFigure 3
  • EP2242759B1 patent drawing

AI summary

Diazaspiro [5.5] undecane derivatives and related compounds as muscarinic-receptor antagonists and beta-adrenoceptor agonists for the treatment of pulmonary disorders.