Pyrido(3,2-d)pyrimidine Derivatives for HCV Replication Inhibition

Solution Overview

Problem

Current treatments for hepatitis C virus (HCV) infections, primarily using pegylated interferon and ribavirin, have significant side effects and high treatment costs, and there is a need for alternative compounds with high HCV replication inhibiting activity that are free from these drawbacks.

Innovation Solution

Development of specific pyrido(3,2-d)pyrimidine derivatives with unique substituents on positions 2, 4, and 6, which exhibit significant antiviral activity against HCV, including compounds represented by structural formula (I), that can be used in pharmaceutical compositions to prevent or treat HCV infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If pegylated interferon and ribavirin are used to treat HCV infections, then antiviral activity is achieved, but significant side effects and high treatment costs occur

Engineering Contradiction:

Improveantiviral activityVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by developing novel pyrido(3,2-d)pyrimidine derivatives with specific molecular structures (formula I) that differ from conventional interferon and ribavirin. The compounds feature variations in substituent groups at positions 2, 4, and 6 of the pyrido(3,2-d)pyrimidine core, creating new chemical entities with potentially improved therapeutic profiles including reduced side effects while maintaining antiviral activity against HCV

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by creating complex molecular structures that combine the pyrido(3,2-d)pyrimidine core with various substituent groups (R1-R7) including aryl, heteroaryl, alkyl, and functional groups. This composite molecular architecture allows for optimized binding affinity to HCV targets while reducing off-target effects that cause side effects

Inventive Principle:

Principle #40Composite materials

2Reliability

If pegylated interferon and ribavirin are used to treat HCV infections, then antiviral activity is achieved, but treatment costs increase

Engineering Contradiction:

Improveantiviral activityVSAvoidtreatment cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by developing novel pyrido(3,2-d)pyrimidine derivatives with specific molecular structures (formula I) that differ from conventional interferon and ribavirin. The compounds feature variations in substituent groups at positions 2, 4, and 6 of the pyrido(3,2-d)pyrimidine core, creating new chemical entities with potentially improved therapeutic profiles including reduced side effects while maintaining antiviral activity against HCV

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent suggests using small molecule antiviral agents (pyrido(3,2-d)pyrimidine derivatives) that can be synthesized more economically than biologics like pegylated interferon. These small molecules typically have simpler manufacturing processes, better stability, and lower production costs, making them more economically viable for long-term HCV treatment

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If existing HCV treatments are used, then viral replication is inhibited, but treatment duration and complexity increase

Engineering Contradiction:

Improveviral replication inhibitionVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies the extraction principle by developing a single novel antiviral compound (pyrido(3,2-d)pyrimidine derivative) that targets HCV replication. This monotherapy approach extracts the antiviral function from the complex combination therapy of interferon plus ribavirin, potentially simplifying treatment regimens while maintaining efficacy through the optimized molecular structure that specifically inhibits HCV replication

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS8143394B2Pyrido(3,2-d)pyrimidines useful for treating viral infections

Publication Date: 2012.03.27 GILEAD SCIENCES INC

AI summary

2-amino-pyrido(3,2-d)pyrimidine derivatives with a specific substitution pattern on positions 4 and 6 of the core structure are useful in the treatment or prevention of an infection due to a virus from the Flaviviridae family, especially HCV, when administered to a patient in a therapeutically effective amount.