M1 Receptor Antagonists for Selective Neurological Treatment
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Solution Overview
Problem
Current treatments for epileptic disorders and movement disorders such as Parkinson's disease lack highly selective muscarinic acetylcholine M1 receptor antagonists that can effectively target the M1 mAChR for therapeutic benefit.
Innovation Solution
Development of compounds and compositions that act as antagonists of the muscarinic acetylcholine M1 receptor, specifically designed to inhibit M1 receptor activity, with structures defined by Formulas (IA) and (I), and their use in pharmaceutical compositions for therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for epileptic disorders and movement disorders are used, then therapeutic benefit is provided, but highly selective M1 receptor antagonism is not achieved
Solution Approach 1:
The patent applies local quality by designing compounds with specific structural features at particular positions to achieve selective M1 receptor binding. The substituents R1-R6 at different positions on the core structure are carefully selected to optimize interaction with M1 receptor-specific amino acid residues, providing local molecular characteristics that confer selectivity while maintaining therapeutic efficacy
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters such as substituent types (R1-R6), chain lengths (m, n, p), and ring structures to optimize both selectivity and therapeutic benefit. Different embodiments explore parameter space to identify compounds with enhanced M1 selectivity compared to prior art treatments
2Reliability
If M1 receptor activity is inhibited, then therapeutic benefits for epileptic disorders and movement disorders are achieved, but treatment specificity is limited by lack of selective antagonists
Solution Approach 1:
The patent applies segmentation by dividing the molecular structure into distinct functional segments: a core structure and multiple substitutable positions (R1-R6). This segmentation allows independent optimization of different molecular regions to achieve both M1 selectivity and therapeutic efficacy, enabling the compound to specifically target M1 receptors while maintaining adaptability for treating various disorders
Solution Approach 2:
The patent achieves universality by designing a core structure with multiple substitutable positions that can be configured to treat different conditions. The same basic compound framework can be adapted for epileptic disorders, Parkinson's disease, dystonia, and fragile X syndrome by modifying substituents, providing a universal platform for treating multiple movement and neurological disorders with high M1 selectivity
Data Source
AI summary
Provided herein are compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.