Cyclic Urea Thiazolyl Compounds Targeting HSV Helicase-Primase

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Solution Overview

Problem

Current treatments for herpes simplex virus (HSV) infections, such as nucleoside analogues, are inadequate in preventing recurrent outbreaks and have adverse effects, and there is a need for improved antiviral compounds with better safety, potency, selectivity, and bioavailability.

Innovation Solution

Development of cyclic urea thiazolyl compounds that inhibit the viral helicase-primase complex, offering a novel mechanism of action against HSV1 and HSV2, including tetra-substituted urea structures with a 6-membered core ring, enhancing biological activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nucleoside analogues are used to treat HSV infections, then viral replication is inhibited, but recurrent outbreaks are not completely prevented and adverse effects increase at high doses

Engineering Contradiction:

Improveprevention of recurrent outbreaksVSAvoidadverse effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical structure parameters from acyclic to cyclic urea compounds, which fundamentally alters the pharmacological properties. This structural parameter change results in improved potency with lower doses required, thereby reducing adverse effects while maintaining or improving prevention of recurrent outbreaks

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention combines multiple functional groups (cyclic urea, thiazolyl, heterocyclic moieties) into a composite molecular structure that targets viral helicase-primase complex. This composite structure provides enhanced antiviral activity and selectivity, improving reliability of outbreak prevention while minimizing harmful effects through better selectivity

Inventive Principle:

Principle #40Composite materials

2Reliability

If high doses of nucleoside analogues are administered to prevent recurrent outbreaks, then viral replication is better controlled, but adverse effects increase

Engineering Contradiction:

Improvecontrol of viral replicationVSAvoidadverse effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs parameter changes by developing cyclic urea compounds with optimized molecular weight, lipophilicity, and metabolic stability. These parameter optimizations enable effective viral replication control at lower doses, thereby reducing adverse effects associated with high-dose nucleoside analogue therapy

Inventive Principle:

Principle #35Parameter changes

3Reliability

If acyclic urea compounds are used as antiviral agents, then viral replication is inhibited, but biological activity is insufficient compared to cyclic structures

Engineering Contradiction:

Improveantiviral activityVSAvoidmolecular structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by cyclizing the urea structure to form rigid cyclic frameworks. This structural parameter change enhances biological activity through improved binding affinity and metabolic stability, while the systematic approach to cyclic structure design manages complexity in a controlled manner

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260103471A1Cyclic urea thiazolyl compounds for treatment of hsv

Publication Date: 2026.04.16 ASSEMBLY BIOSCIENCES INC

AI summary

The present disclosure provides, in part, cyclic urea thiazolyl compounds, and pharmaceutical compositions thereof, and methods of the treatment and prophylaxis of HSV infections.