TLR7 TLR8 Modulator Compounds Specificity

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Solution Overview

Problem

Current methods for modulating Toll-Like Receptors (TLRs) lack effective compounds that can specifically target and modulate these receptors, particularly TLR7 and TLR8, for treating various diseases and disorders.

Innovation Solution

Development of specific compounds, such as those represented by Formula (I-A), which are designed to modulate TLR receptors by administering therapeutically effective amounts of these compounds or their pharmaceutically acceptable salts, thereby acting as TLR receptor agonists or antagonists to treat conditions like infectious diseases, inflammatory diseases, and autoimmune disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing methods for modulating TLRs are used, then general immune modulation may be achieved, but specific targeting of TLR7 and TLR8 receptors is insufficient

Engineering Contradiction:
Improvespecificity of TLR modulationVSAvoidrange of diseases treatable
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by designing compounds with specific molecular structures (Formula I) that are tailored to interact with particular TLR subtypes (TLR7 and TLR8) rather than providing non-specific immune modulation. The compounds contain specific functional groups and molecular configurations that confer selective affinity for these receptors, enabling precise modulation at the receptor level while maintaining therapeutic versatility across different disease types.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by systematically varying molecular parameters of the TLR modulators, including substituent groups, molecular weight, and structural configurations. These parameter variations allow the compounds to optimize their binding affinity and efficacy for TLR7 and TLR8 while maintaining pharmacokinetic properties suitable for treating diverse diseases, thereby resolving the contradiction between specificity and versatility.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If TLR modulators are developed to treat multiple disease types, then versatility is improved, but compound complexity increases

Engineering Contradiction:
Improverange of diseases treatableVSAvoidcompound structure complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies universality by designing a core molecular scaffold (Formula I) that can serve multiple therapeutic functions. The compounds are capable of modulating TLR7 and TLR8 receptors in different disease contexts, including viral infections, bacterial infections, inflammatory conditions, and autoimmune disorders. This multi-functional capability is achieved through a unified structural platform that can be adapted for various indications without requiring entirely different compound classes.

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

Solution Approach 2:

The patent utilizes segmentation by dividing the molecular structure into distinct functional components: a core scaffold and variable substituent groups. This segmentation allows independent optimization of different regions - the core structure provides the essential TLR binding capability, while substituent groups can be adjusted to fine-tune specificity, pharmacokinetics, and tissue distribution. This modular approach reduces overall complexity compared to designing entirely new compounds for each disease indication.

Inventive Principle:
Principle #1Segmentation

3Reliability

If therapeutically effective amounts of TLR modulators are administered, then disease treatment efficacy is improved, but potential harmful effects increase

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidadverse immune effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies the inversion principle by considering both agonist and antagonist activities within the same molecular framework. Rather than only stimulating TLRs to enhance immunity, the compounds can also block TLR signaling to prevent excessive immune activation. This dual capability allows the same structural class to treat conditions requiring immune enhancement (infections) and conditions requiring immune suppression (autoimmune disorders), thereby managing harmful effects while maintaining therapeutic efficacy.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent utilizes feedback mechanisms by designing compounds that can be regulated based on disease state and patient response. The modular structure allows for dose adjustment and combination therapies that respond to therapeutic outcomes. Feedback control is implemented through monitoring of immune activation markers and clinical response, enabling dynamic optimization of the therapeutically effective amount to maximize benefit while minimizing harmful effects.

Inventive Principle:
Principle #23Feedback

Data Source

PatentEP2268618B1Compounds and compositions as TLR activity modulators
Publication Date: 2015.05.27 NOVARTIS AG
  • EP2268618B1 patent drawingFigure 1
  • EP2268618B1 patent drawingFigure 2
  • EP2268618B1 patent drawingFigure 3

AI summary

The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors, including TLR7 and TLR8. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness of a vaccine (formula I) wherein: X3 is N; X4 is N Or CR3; X5 is -CR4=CR5.