Bicyclic Phenyl Piperidine Modulators for Muscarinic Receptor Selectivity
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Solution Overview
Problem
Current muscarinic receptor modulators lack subtype selectivity, leading to non-specific activation of the parasympathetic nervous system and increased adverse effects, limiting their therapeutic efficacy and safety for treating muscarinic receptor-mediated diseases.
Innovation Solution
Development of specific compounds, such as those represented by formula I, which selectively modulate muscarinic receptors M1-M5 by interacting with them to either increase or decrease their activity, thereby providing subtype-selective agonist or antagonist effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If non-selective muscarinic receptor modulators are used, then broad therapeutic coverage is achieved, but subtype selectivity deteriorates leading to increased adverse effects
Solution Approach 1:
The patent segments the muscarinic receptor modulation by designing compounds with specific structural features that target individual receptor subtypes (M1-M5). The general formula I structure with variable substituents R1-R10 allows differentiation between subtypes through specific chemical modifications, enabling selective binding to particular receptor subtypes while maintaining therapeutic efficacy.
Solution Approach 2:
The patent applies local quality by introducing specific substituent patterns at particular positions on the core structure. Different substituents at R1-R10 positions create local chemical environments that preferentially interact with specific receptor subtype binding sites, thereby achieving subtype selectivity while maintaining overall compound stability and pharmacological activity.
2Object-affected harmful factors
If subtype-selective compounds are developed, then adverse effects are reduced, but manufacturing complexity increases
Solution Approach 1:
The patent utilizes parameter changes by systematically varying substituent types, positions, and configurations on the core structure to achieve subtype selectivity. These controlled modifications allow for rational drug design where each substituent change can be correlated with specific receptor subtype preferences, enabling selective modulation without requiring complete structural redesign.
Data Source
AI summary
The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.