Fused Cyclic HCMV Compounds Resolving Toxicity and Bioavailability Trade-offs
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Solution Overview
Problem
Current antiviral drugs for human cytomegalovirus (HCMV) infections, such as ganciclovir, foscavir, and cidofovir, are limited by severe toxic side effects, low oral bioavailability, and the risk of drug resistance, necessitating the development of safer and more effective treatments.
Innovation Solution
A compound represented by formula (I) or (II) and its pharmaceutically acceptable salts or tautomers, which are fused cyclic compounds, are used to prevent HCMV infections by offering reduced toxic side effects, improved oral bioavailability, and a lower risk of drug resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antiviral drugs (ganciclovir, foscavir, cidofovir) are used to treat HCMV infections, then antiviral efficacy is achieved, but severe toxic side effects occur
Solution Approach 1:
The patent modifies the chemical structure of ganciclovir by replacing the hydrogen atom at position 5 of the pyrimidine ring with a fused cyclic group (cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl ring). This structural parameter change reduces toxic side effects while maintaining antiviral efficacy against HCMV infections.
Solution Approach 2:
The invention creates composite molecular structures by combining the ganciclovir core with fused cyclic groups, forming new compounds that integrate the antiviral properties of ganciclovir with the structural stability and reduced toxicity of cyclic hydrocarbon groups.
2Ease of operation
If current antiviral drugs are administered orally, then treatment convenience is improved, but oral bioavailability remains low
Solution Approach 1:
The fused cyclic groups introduced into the ganciclovir structure improve oral bioavailability by modifying pharmacokinetic parameters, enhancing absorption and metabolism properties while maintaining the ability to administer the drug orally for convenient treatment.
3Reliability
If viral DNA polymerase inhibitors are used to treat HCMV, then antiviral activity is achieved, but drug resistance develops due to mutations
Solution Approach 1:
By modifying the chemical structure of ganciclovir with fused cyclic groups, the patent creates compounds with altered binding characteristics to viral DNA polymerase, reducing the likelihood of resistance development through mutations while maintaining effective antiviral activity.
Data Source
AI summary
Disclosed are a class of fused cyclic compounds against the HCMV virus, and use thereof in the preparation of a drugs for treating diseases associated with the HCMV virus. In particular, disclosed is the compound shown in formula (II) and pharmaceutically acceptable salts thereof.