Ethynyl Derivatives as mGluR5 Allosteric Modulators
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Solution Overview
Problem
There is a scarcity of selective allosteric modulators for the metabotropic glutamate receptor subtype 5 (mGluR5) that effectively address neurological disorders with minimal CNS-related side effects, as conventional modulators often have high efficacy leading to severe side effects.
Innovation Solution
Development of ethynyl derivatives of formula I, which are allosteric modulators of mGluR5, showing efficacies below 60% and thus reducing the risk of severe CNS side effects, while maintaining therapeutic effects at higher doses compared to structurally similar compounds in prior art.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional mGluR5 modulators are used to achieve therapeutic effects, then the desired therapeutic effect is obtained, but severe CNS-related side effects occur due to high efficacy
Solution Approach 1:
The patent changes the efficacy parameter of the allosteric modulator from high (>60%) to low (<60%) to resolve the contradiction. This parameter change allows the compound to maintain therapeutic effects while reducing the severity of CNS side effects, creating a safer therapeutic profile for mGluR5-mediated disorders.
2Power
If high efficacy allosteric modulators are used, then strong therapeutic effects are achieved, but the therapeutic window narrows due to side effects at close dosing ranges
Solution Approach 1:
The patent applies parameter change by reducing the efficacy of the allosteric modulator to below 60%, which widens the therapeutic window. This allows for a broader dosing range where therapeutic effects are maintained without triggering severe CNS side effects, improving the adaptability and safety margin of the treatment.
3Reliability
If selective allosteric modulators for mGluR5 are developed, then neurological disorders can be treated, but scarcity of such selective compounds limits availability
Solution Approach 1:
The patent segments the allosteric modulator market by developing compounds with specific structural features (ethynyl derivatives of formula I) that provide selective binding to mGluR5. This segmentation approach creates a distinct class of selective modulators with reduced side effects, increasing the quantity and diversity of available therapeutic options for mGluR5-mediated disorders.
Data Source
AI summary
The present invention relates to ethynyl derivatives of formula (I) wherein R1 is phenyl, which is optionally substituted by 1-2 halogen atoms; selected from fluorine or chlorine; or to a pharmaceutically acceptable acid addition salt in enantiomerically pure form. It has been found that the compounds of general formula (I) are allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5).