Abstract
A series of phenyloxyethyl and cinnamyl derivatives of substituted uracils were synthesized and found to exhibit potent activity against HIV-RT and HIV replication in cell culture. In general, the cinnamyl derivatives proved superior to the phenyloxyethyl derivatives, however 1-[2-(4-methylphenoxy)ethyl]-3-(3,5-dimethylbenzyl)uracil (19) exhibited the highest activity (EC(50)=0.27 μM) thus confirming that the 3-benzyluracil fragment in the NNRTI structure can be regarded as a functional analogue of the benzophenone pharmacophore typically found in NNRTIs.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line
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Cinnamates / chemistry
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / genetics
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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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Humans
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Molecular Docking Simulation
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Mutation
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Protein Structure, Tertiary
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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
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Uracil / analogs & derivatives*
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Uracil / chemical synthesis
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Uracil / pharmacology
Substances
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Cinnamates
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Reverse Transcriptase Inhibitors
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Uracil
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase