Abstract
Starting from the prototypic compound 4, we describe new, potent, and broad-spectrum pyrrolobenzo(pyrido)oxazepinones antivirals. A biochemical and enzymological investigation was performed for defining their mechanism of inhibition at either recombinant HIV-1 RT wild type and non-nucleoside reverse transcriptase inhibitors (NNRTIs)-resistant mutants. For the novel compounds (S)-(+)-5 and (S)-(-)-7, a clear-cut stereoselective mechanism of enzyme inhibition was found. Molecular modeling studies were performed for revealing the underpinnings of this behavior.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / pharmacology
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Conserved Sequence
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Drug Resistance / drug effects*
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Drug Resistance / genetics
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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 / enzymology
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HIV-1 / genetics
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Humans
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Models, Molecular
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Mutation
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Reverse Transcriptase Inhibitors / chemistry*
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Reverse Transcriptase Inhibitors / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anti-HIV Agents
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Reverse Transcriptase Inhibitors
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase