Cyclic Phosphate Nucleosides Inhibit HCV NS5B Polymerase

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Solution Overview

Problem

Current treatments for Hepatitis C virus (HCV) infection are inadequate, with chronic infection remaining a major healthcare concern and no established vaccine available.

Innovation Solution

Development of Cyclic Phosphate Substituted Nucleoside Compounds, which are designed to inhibit HCV viral replication by targeting the NS5B polymerase, thereby treating or preventing HCV infection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current HCV treatments are used, then some viral inhibition is achieved, but chronic infection remains and treatment effectiveness is inadequate

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidviral replication inhibition

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of nucleoside compounds to create cyclic phosphate substituted derivatives. This structural modification changes the pharmacological parameters of the compounds, enhancing their ability to inhibit HCV NS5B polymerase and achieve sustained virologic response in chronically infected patients

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses composite materials by combining cyclic phosphate groups with nucleoside structures to create hybrid compounds. These composite nucleoside compounds integrate the antiviral properties of nucleosides with the enhanced stability and activity of cyclic phosphate groups, resulting in improved treatment effectiveness against HCV

Inventive Principle:

Principle #40Composite materials

2Reliability

If HCV infection is left untreated, then natural virus clearance occurs in 20% of cases, but 80% of patients develop chronic infection leading to cirrhosis and cancer

Engineering Contradiction:

Improvevirus clearance rateVSAvoidliver disease progression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by administering cyclic phosphate substituted nucleoside compounds to prevent HCV infection progression before chronic disease develops. The compounds act preemptively to inhibit viral replication early in the infection course, preventing the development of cirrhosis and hepatocellular carcinoma that would otherwise occur in untreated patients

Inventive Principle:

Principle #10Preliminary action

3Adaptability or versatility

If no vaccine is available for HCV, then prevention through immunization is impossible, but treatment options remain limited

Engineering Contradiction:

Improveprevention capabilityVSAvoidtherapeutic agent development

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent uses intermediary compounds by developing cyclic phosphate substituted nucleosides that act as mediators between the host cell and HCV polymerase. These intermediary compounds compete with natural nucleosides for incorporation into viral RNA, thereby inhibiting viral replication without requiring vaccine-induced immunity

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP3471737B1Cyclic phosphate substituted nucleoside compounds and methods of use thereof for the treatment of viral diseases

Publication Date: 2025.06.04 MERCK SHARP & DOHME LLC

AI summary

The present invention relates to Cyclic Phosphate Substituted Nucleoside Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, R1, R2, R3, Q and V are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Compound, and methods of using the Cyclic Phosphate Substituted Nucleoside Compounds for treating or preventing HCV infection in a patient.