Squaric Derivatives Targeting HCV NS5B Protein

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Solution Overview

Problem

Current treatments for hepatitis C virus (HCV) infection are limited by the lack of effective vaccines and therapies, particularly for genotype 1 HCV, with only approximately 50% of patients achieving sustained virologic response and experiencing severe side effects from existing treatments.

Innovation Solution

Development of novel compounds of Formula I, including pharmaceutically acceptable salts, which demonstrate activity against HCV, specifically targeting the NS5B protein to inhibit viral replication and infection, and are formulated into pharmaceutical compositions for effective treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current HCV treatments (pegylated alpha-interferon and ribavirin) are used, then viral infection is targeted, but treatment efficacy is limited and severe side effects occur

Engineering Contradiction:

Improvetreatment efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs parameter changes by developing novel chemical compounds with modified molecular structures (Formula I with various substituents R1-R8) to achieve improved antiviral activity and reduced side effects compared to existing therapies

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses intermediaries by designing compounds that target specific HCV proteins (NS5A, NS5B, protease) as mediators to inhibit viral replication, thereby achieving antiviral effects with potentially better safety profiles

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If genotype-specific treatments are developed, then treatment precision is improved, but device complexity and development difficulty increase

Engineering Contradiction:

Improvegenotype targeting precisionVSAvoidcompound structure complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies universality by designing compounds of Formula I with multiple substituent options (R1-R8) that can be optimized for different HCV genotypes, allowing a single compound framework to serve multiple genotype-specific treatment needs

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS9624180B2Squaric derivatives for the treatment of hepatitis C

Publication Date: 2017.04.18 BRISTOL MYERS SQUIBB CO

AI summary

Compounds of Formula I, including pharmaceutically acceptable salts thereof, are set forth, in addition to compositions and methods of using these compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.