N(1),N(3)-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase

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)=0.27μM) 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.publisher: Elsevier articletitle: N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2012.12.027 content_type: article copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.status: publishe