Pyrazolopyrimidine Derivatives as mGluR5 Modulators

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Solution Overview

Problem

Current treatments for neurological and CNS disorders related to abnormal glutamate neurotransmission lack effective modulators for metabotropic glutamate receptors, particularly mGluR5, which are crucial for therapeutic benefits in various diseases.

Innovation Solution

Development of novel pyrazolopyrimidine derivatives that act as potent mGluR5 modulators, administered as pharmaceutical compositions to modulate glutamate neurotransmission and treat a wide range of neurological and CNS disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for neurological disorders, then existing therapies are administered, but they lack effective modulators for metabotropic glutamate receptors (mGluR5)

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidreceptor modulation capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops novel pyrazolopyrimidine derivatives with specific molecular structures (formula I) that fundamentally change the chemical parameters of mGluR5 modulators. These compounds exhibit potent modulatory activity at mGluR5 receptors with selective binding characteristics, thereby improving therapeutic effectiveness for neurological disorders while enhancing adaptability to target specific receptor subtypes.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If pyrazolopyrimidine derivatives are developed as mGluR5 modulators, then neuroprotection and therapeutic benefits are achieved, but the complexity of drug development and clinical validation increases

Engineering Contradiction:
Improveneuroprotection efficacyVSAvoiddrug development complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary pharmacological characterization and preclinical validation of pyrazolopyrimidine derivatives before clinical application. The compounds have been tested in relevant in vitro and in vivo models to demonstrate neuroprotective effects and mGluR5 modulatory activity, thereby reducing development risks and streamlining the path to clinical trials for neurological disorders.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If mGluR5 modulators are administered for neurological disorders, then cognitive functions and neurological conditions are improved, but the scope of applicable diseases and conditions expands requiring broader validation

Engineering Contradiction:
Improvedisease indication rangeVSAvoidvalidation time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The pyrazolopyrimidine derivatives demonstrate broad-spectrum applicability across multiple neurological and psychiatric disorders by targeting mGluR5 receptors that are widely distributed in the CNS. The compounds show efficacy in Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy, and other conditions, allowing a single therapeutic agent to address multiple disease indications simultaneously, thereby reducing overall validation time through shared clinical trial frameworks.

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

Data Source

PatentEP2054416B8Substituted pyrazolopyrimidines, a process for their preparation and their use as medicine
Publication Date: 2014.07.16 MERZ PHARMA GMBH & CO KGAA

AI summary

Substituted pyrazolopyrimidine derivatives of formula (I) wherein Y1, Y2, Y3, Y4 represent N or C-, whereby at least two of the groups Y1 to Y4 denote a carbon atom, R1 represents chloro or bromo, R2 to R7 represent e.g. hydrogen, methyl or ethyl; and R10 and R11 independent ly represent e.g. hydrogen or C1-C6alkyl, are potent mGluR5 modulators and are useful for the prevention of acute and chronic neurological disorders.