Abstract
A series of raltegravir derivatives 20-42 were prepared and systematically evaluated for their anti-HIV activity. The bioassay results showed that most of the compounds possess good to excellent anti-HIV activity. Especially, compounds 25 and 35 with subpicomole IC(50) values seemed to be the most potent anti-HIV agents among all of the reported synthesized compounds. These compounds may therefore be considered as new potent anti-HIV agents. The 5-hydroxyl modification of raltegravir derivatives significantly increased the anti-HIV activity, which indicates that the hydroxyl may not be indispensable for raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is favorable for antiviral activity. In addition, a high-throughput cell-based assay method with pseudotyped virus stocks was developed and used to identify HIV inhibitors.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology*
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Benzoates / chemical synthesis*
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Benzoates / pharmacology*
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Cell Proliferation / drug effects
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Cells, Cultured
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Drug Design*
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HIV Infections / drug therapy*
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HIV-1 / drug effects*
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Humans
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Molecular Structure
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / pharmacology*
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Pyrimidinones / chemical synthesis*
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Pyrimidinones / pharmacology*
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Pyrrolidinones / pharmacology*
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Raltegravir Potassium
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Reverse Transcriptase Inhibitors / chemical synthesis
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
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Virus Replication / drug effects
Substances
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2-(2-(2-(diethylamino)-2-oxoacetamido)propan-2-yl)-4-(4-fluorobenzylcarbamoyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-5-yl benzoate
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4-(4-fluorobenzylcarbamoyl)-1-methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl benzoate
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Anti-HIV Agents
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Benzoates
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Oxadiazoles
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Pyrimidinones
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Pyrrolidinones
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Reverse Transcriptase Inhibitors
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Raltegravir Potassium