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. 2013 Mar 1;21(5):1150-8.
doi: 10.1016/j.bmc.2012.12.027. Epub 2013 Jan 3.

N1,N3-disubstituted Uracils as Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase

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N1,N3-disubstituted Uracils as Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase

Mikhail S Novikov et al. Bioorg Med Chem. .
Free PMC article

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.

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Predicted binding modes for 19 overlaid with original ligands (pale-yellow colored) in 3DYA (left) and 3DOK (right) crystal structures. Only key residues are shown. Orange lines indicate stacking interactions.

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