Abstract
Using 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3(2H)-dione based HIV-1 integrase inhibitors as display platforms, we undertook a thorough examination of the effects of modifying the halogen substituents on a key benzyl ring that is hypothesized to bind in a hydrophobic pocket of the integrase.DNA complex. Data from this study suggest that in general dihalo-substituted analogues have higher potency than monohalo-substituted compounds, but that further addition of halogens is not beneficial.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Cells, Cultured
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HIV Integrase / chemistry
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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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Halogens / chemical synthesis
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Halogens / chemistry*
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Humans
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Isoindoles / chemical synthesis
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Isoindoles / chemistry*
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Isoindoles / pharmacology
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Structure-Activity Relationship
Substances
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HIV Integrase Inhibitors
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Halogens
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Isoindoles
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HIV Integrase
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p31 integrase protein, Human immunodeficiency virus 1