1,2,4-Triazine Derivatives as TLR7/8 Modulators

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Solution Overview

Problem

Current Toll-Like Receptor modulators lack selectivity, potency, metabolic stability, and safety, making them inadequate for effective treatment of viral infections and immune disorders.

Innovation Solution

Development of 1,2,4-triazine derivatives with specific alkyl, arylalkyl, or heteroarylalkyl substitutions that act as modulators of TLR7 and/or TLR8, offering improved selectivity, potency, and metabolic stability, formulated into pharmaceutical compositions for treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing Toll-Like Receptor modulators are used, then some antiviral activity is achieved, but selectivity, potency, and safety are insufficient

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidsafety profile

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of existing TLR modulators by changing molecular parameters - specifically introducing 1,2,4-triazine core structures with varied substituents (R1-R6 groups). This structural parameter change results in compounds with improved selectivity for TLR7 and TLR8, higher potency (lower IC50 values), and better safety profiles compared to prior art compounds.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures combining the 1,2,4-triazine core with various functional groups and substituents. These composite structures allow optimization of multiple properties simultaneously - the triazine core provides TLR modulation activity while attached groups tune selectivity, potency, and safety characteristics.

Inventive Principle:

Principle #40Composite materials

2Reliability

If existing Toll-Like Receptor modulators are used, then some antiviral activity is achieved, but metabolic stability is insufficient

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidmetabolic stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent systematically varies molecular parameters in the TLR modulator structure, particularly the substituents R1-R6 on the 1,2,4-triazine core. This parameter optimization results in compounds with enhanced metabolic stability, as evidenced by improved half-life and reduced clearance rates compared to existing modulators.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If existing Toll-Like Receptor modulators are used, then some activity is achieved, but selectivity for specific TLRs is insufficient

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidselectivity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality modification by introducing specific functional groups and substituents at particular positions on the 1,2,4-triazine core structure. Different R1-R6 groups provide selective binding to specific TLR subtypes (particularly TLR7 and TLR8), enabling tailored therapeutic effects for different viral infections while minimizing off-target effects.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS9416114B21,2,4-triazine derivatives for the treatment of viral infections

Publication Date: 2016.08.16 CENT NAT DE LA RECH SCI (C N R S)

AI summary

This invention relates to 1,2,4-triazine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.