Abstract
New tricyclic HIV-1 integrase (IN) inhibitors were prepared that combined structural features of bicyclic pyrimidinones with recently disclosed 4,5-dihydroxy-1H-isoindole-1,3(2H)-diones. This combination resulted in the introduction of a nitrogen into the aryl ring and the addition of a fused third ring to our previously described inhibitors. The resulting analogues showed low micromolar inhibitory potency in in vitro HIV-1 integrase assays, with good selectivity for strand transfer relative to 3'-processing.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Biological Assay
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Cells, Cultured
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Cyclization
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HIV Integrase / metabolism
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HIV Integrase Inhibitors / chemical synthesis*
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HIV Integrase Inhibitors / chemistry*
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HIV Integrase Inhibitors / pharmacology
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HIV-1 / drug effects
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HIV-1 / enzymology*
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Humans
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Hydroxylation
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Inhibitory Concentration 50
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Molecular Structure
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Pyrimidinones / chemical synthesis*
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Pyrimidinones / chemistry
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Pyrimidinones / pharmacology
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Structure-Activity Relationship
Substances
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HIV Integrase Inhibitors
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Pyrimidinones
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HIV Integrase
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p31 integrase protein, Human immunodeficiency virus 1