Sulfonyl-quinoline derivatives for mGluR1 and mGluR5 receptor modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current compounds do not effectively target mGluR1 and mGluR5 receptors for therapeutic modulation in neurological and psychiatric disorders, acute and chronic pain, and neuromuscular dysfunctions, lacking specificity and potency.
Innovation Solution
Development of new mGluR1 and mGluR5 receptor subtype preferring ligands of formula (I), including phenyl and thienyl groups with specific substituents, which form salts, hydrates, and solvates, for use in pharmaceutical compositions to modulate these receptors therapeutically.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds are used for mGluR1 and mGluR5 receptor modulation, then therapeutic application is possible, but potency and selectivity are insufficient
Solution Approach 1:
The patent applies local quality by introducing specific substituent patterns at defined positions on the quinoline core structure. Different substituents (halogens, alkyl groups, aryl groups, heteroaryl groups) are placed at specific positions (R1-R6) to optimize interaction with specific receptor subtypes, thereby achieving both potency and selectivity simultaneously
Solution Approach 2:
The patent employs parameter changes by systematically varying chemical parameters including substituent types, substituent positions, and molecular weight ranges. This allows optimization of the compounds' binding affinity and selectivity for mGluR1 versus mGluR5 receptors while maintaining therapeutic efficacy
2Ease of manufacture
If compound structure is simplified for ease of manufacture, then production becomes easier, but receptor binding potency decreases
Solution Approach 1:
The patent applies segmentation by dividing the molecule into distinct functional modules: a quinoline core structure with independently variable substituent groups (R1-R6). This modular approach allows each position to be optimized for binding while maintaining overall structural simplicity that facilitates synthesis through sequential, independent steps
Solution Approach 2:
The patent employs universality by designing a core quinoline structure that serves multiple functions: providing structural rigidity for binding, offering multiple substitution positions for optimization, and maintaining chemical stability. This universal scaffold supports diverse substituent combinations without requiring complete resynthesis of the core structure
Data Source
AI summary
New mGluRl and mGluR5 receptor subtype preferring ligands of formula: (I) and/or salts and/or hydrates and/or solvates thereof, to the processes and intermediates for their preparation, to pharmaceutical compositions containing these compounds and to their use in therapy and/or prevention of a condition which requires modulation of mGluRl and mGluR5 receptors.FORMULE (I) wherein Ar1 represents an optionally substituted phenyl or heteroaryl group; Ar2 represents a substituted phenyl or an optionally substituted heteroaryl group; R1, R2, R3 and R4 represent independently a substituent selected from hydrogen, halogen, cyano, alkyl, alkoxy, hydroxy, trifluoromethyl, amino, alkylamino, dialkylamino, aminomethyl, alkylaminomethyl, dialkylaminomethyl