Abstract
3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1. It was found that several compounds were potent inhibitors of HIV-1 with the most potent compound 24 exhibiting an IC90 = 32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC90s against several clinically meaningful mutant virus strains.
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology
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Combinatorial Chemistry Techniques
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Cytopathogenic Effect, Viral / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Fluorine / chemistry
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / genetics
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HIV-1 / drug effects
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HIV-1 / genetics
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Inhibitory Concentration 50
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Mutation
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Pyridones / chemical synthesis
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Pyridones / pharmacology*
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Structure-Activity Relationship
Substances
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Anti-HIV Agents
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Enzyme Inhibitors
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Pyridones
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Fluorine
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HIV Reverse Transcriptase