Isoxazoles with antipicornavirus activity
Journal of Medicinal Chemistry
|June 1, 1985
Summary
New isoxazole compounds show promise as antiviral agents. Compound 32 effectively combats rhinovirus and poliovirus in vitro and improves survival rates in infected mice.
Area of Science:
- Medicinal Chemistry
- Virology
- Pharmacology
Background:
- Picornaviruses, including rhinoviruses and polioviruses, are significant human pathogens.
- Developing effective antiviral therapies against these viruses remains a critical challenge.
Purpose of the Study:
- To synthesize and evaluate novel 3,5-disubstituted isoxazoles as potential antipicornavirus agents.
- To identify compounds with potent in vitro activity against rhinovirus and poliovirus.
Main Methods:
- Synthesis of a series of 3,5-disubstituted isoxazole compounds.
- In vitro antiviral assays against rhinovirus type 2 and poliovirus type 2.
- In vivo evaluation of lead compounds in a mouse model of poliovirus infection.
Main Results:
- Several synthesized isoxazoles demonstrated significant in vitro efficacy against rhinovirus type 2 and poliovirus type 2.
- Compound 32 exhibited superior activity compared to the known agent 4',6-dichloroflavan.
- Oral administration of compound 32 in mice infected with poliovirus-2 resulted in a 53% survival rate, significantly higher than the 22% in control animals.
Conclusions:
- 3,5-disubstituted isoxazoles represent a promising class of compounds for antipicornavirus drug development.
- Compound 32 warrants further investigation as a potential therapeutic agent for picornavirus infections.
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