Abstract
GW4511, GW4751, and GW3011 showed IC50 values < or =2 nM against wild type HIV-1 and <10 nM against 16 mutants. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. The antiviral data together with the favorable pharmacokinetic data of GW4511 suggested that these benzophenones possess attributes of a new NNRTI drug candidate.
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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Benzophenones / chemical synthesis*
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Benzophenones / chemistry
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Benzophenones / pharmacology
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Cell Line
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Crystallography, X-Ray
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Drug Resistance, Viral
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / chemistry
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HIV Reverse Transcriptase / metabolism
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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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Inhibitory Concentration 50
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Mutation
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Protein Binding
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Anti-HIV Agents
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Benzophenones
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Reverse Transcriptase Inhibitors
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HIV Reverse Transcriptase