Linked Tricyclic Aryl Compounds for HCV Treatment

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Solution Overview

Problem

Current treatments for Hepatitis C virus (HCV) infection, such as α-interferon monotherapy and combination therapy, suffer from poor efficacy and unfavorable side effects, and there is a need for small-molecule compounds with improved physicochemical properties to inhibit HCV replication and treat related disorders.

Innovation Solution

Development of Linked Tricyclic Aryl Compounds, specifically Compounds of Formula (I), which are designed to inhibit HCV viral replication and treat or prevent HCV infection by targeting specific viral targets, including HCV NS5A, with improved physicochemical properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies (α-interferon monotherapy and combination therapy with ribavirin) are used to treat HCV infection, then some patients show improvement, but the treatment suffers from poor efficacy and unfavorable side effects

Engineering Contradiction:

Improvetreatment efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by developing small-molecule compounds with optimized physicochemical properties (molecular weight, logP, hydrogen bond donors/acceptors) to achieve better therapeutic efficacy and reduced side effects compared to conventional interferon-based therapies. The compounds of Formula (I) represent a systematic modification of molecular parameters to improve the therapeutic index.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention employs composite molecular structures consisting of three linked aryl moieties (A, B, and D) connected through linker groups L1 and L2. This composite structure combines multiple functional groups and aromatic systems to create a molecule that targets HCV replication with enhanced specificity and reduced off-target effects compared to single-component therapies.

Inventive Principle:

Principle #40Composite materials

2Reliability

If small-molecule inhibitors are developed to target specific viral targets, then therapeutic efficacy can be improved, but the complexity of compound design and synthesis increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidcompound structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the inhibitor molecule into three distinct aryl moieties (A, B, and D) that can be independently selected and optimized. Each aryl group can be chosen from specific heterocyclic or aromatic structures, allowing modular design and systematic optimization of binding affinity and selectivity for HCV targets.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention achieves universality by designing a platform compound of Formula (I) where the three aryl moieties and linker groups can be varied to create multiple derivatives targeting different HCV proteins (NS3/4A protease, NS5A, NS5B polymerase). This multi-functional design allows a single molecular framework to address multiple viral targets and potentially different HCV genotypes.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS8980920B2Antiviral compounds of three linked aryl moieties to treat diseases such as hepatitis C

Publication Date: 2015.03.17 MERCK SHARP & DOHME LLC

AI summary

The present invention relates to novel Linked Tricyclic Aryl Compounds, compositions comprising at least one Linked Tricyclic Compound, and methods of using Linked Tricyclic Aryl Compounds for treating or preventing HCV infection in a patient. in one aspect, the present invention provides Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein: Non-limiting examples of the Compounds of Formula (II) include compound 56.