2,3-Substituted Azaindole Derivatives for HCV Protease Inhibition

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Solution Overview

Problem

Current treatments for Hepatitis C virus (HCV) infection are plagued by poor efficacy and unfavorable side effects, and there is a need for non-peptide, small-molecule compounds with improved physicochemical properties to effectively inhibit HCV replication and treat related disorders.

Innovation Solution

Development of 2,3-Substituted Azaindole Derivatives, which are compounds of specific formulas (I and II) and their pharmaceutically acceptable salts, solvates, and prodrugs, designed to inhibit viral infections and virus-related disorders by targeting key viral proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for HCV infection are used, then viral replication is inhibited, but side effects increase and efficacy decreases

Engineering Contradiction:

ImproveefficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of antiviral compounds - specifically transitioning from peptide-based treatments to small-molecule compounds with optimized physicochemical properties. The small-molecule compounds of formula (I) feature specific structural parameters (molecular weight, hydrophobicity, functional groups) that improve cellular penetration and target binding affinity while reducing immunogenicity and off-target effects, thereby resolving the contradiction between efficacy and side effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs small-molecule compounds that are metabolically stable yet designed to be cleared from the body after performing their antiviral function. These compounds achieve high efficacy through potent binding to HCV protease but have favorable pharmacokinetic profiles with appropriate half-lives, avoiding accumulation and chronic toxicity associated with longer-acting treatments

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Reliability

If peptide-based treatments are used, then viral replication is inhibited, but physicochemical properties deteriorate

Engineering Contradiction:

Improveinhibition of viral replicationVSAvoidphysicochemical properties

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent substitutes peptide-based molecular structures with small-molecule chemical structures. This replacement transforms the molecular architecture from complex, flexible peptide chains to rigid, well-defined small molecules with predictable physicochemical behavior. The small-molecule compounds exhibit improved stability, solubility, and membrane permeability while maintaining protease inhibition activity through alternative molecular recognition mechanisms

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If existing HCV treatments are administered, then viral infection is treated, but therapeutic options are limited

Engineering Contradiction:

Improvetherapeutic optionsVSAvoidtreatment efficacy

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent develops small-molecule compounds with broad-spectrum antiviral activity that can treat multiple HCV genotypes and potentially other flaviviral infections. The compounds of formula (I) are designed to target conserved regions of the HCV protease, providing universal inhibition across different viral strains, thereby expanding therapeutic options while maintaining high efficacy and offering alternatives for treatment-resistant cases

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS8404845B22,3-substituted azaindole derivatives for treating viral infections

Publication Date: 2013.03.26 MERCK SHARP & DOHME LLC

AI summary

The present invention relates to 2,3-Substituted Azaindole Derivatives, compositions comprising at least one 2,3-Substituted Azaindole Derivatives, and methods of using the 2,3-Substituted Azaindole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.