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N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase.

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 ?M) 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.

SUBMITTER: Novikov MS

PROVIDER: S-EPMC7125863 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase.

Novikov Mikhail S MS Valuev-Elliston Vladimir T VT Babkov Denis A DA Paramonova Maria P MP Ivanov Alexander V AV Gavryushov Sergey A SA Khandazhinskaya Anastasia L AL Kochetkov Sergey N SN Pannecouque Christophe C Andrei Graciela G Snoeck Robert R Balzarini Jan J Seley-Radtke Katherine L KL

Bioorganic & medicinal chemistry 20130103 5

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 ...[more]

PMID: 23357038

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