Abstract
A series of HIV-1 integrase inhibitors containing a novel metal binding motif consisting of the 8-hydroxy-1,6-naphthyridine core and either an oxadiazole or triazole has been identified. The design of the key structural components was based on a two-metal coordination pharmacophore. This report presents initial structure-activity data that shows the new chelation architecture delivers potent inhibition in both enzymatic and antiviral assays.
MeSH terms
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Amino Acid Motifs
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology
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Chelating Agents / pharmacology
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Chemistry, Pharmaceutical / methods*
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Drug Design
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HIV Infections / drug therapy
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HIV Integrase Inhibitors / chemical synthesis*
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HIV Integrase Inhibitors / pharmacology
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Humans
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Models, Chemical
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Molecular Structure
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Naphthyridines / chemical synthesis*
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Naphthyridines / pharmacology
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Oxadiazoles / chemistry*
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Structure-Activity Relationship
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Triazoles / chemistry*
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Virus Replication / drug effects
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Virus Replication / genetics
Substances
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Anti-HIV Agents
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Chelating Agents
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HIV Integrase Inhibitors
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Naphthyridines
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Oxadiazoles
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Triazoles