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

  • Bioorg Med Chem. 2013 Mar 1;21(5):1150-8. doi: 10.1016/j.bmc.2012.12.027.
Mikhail S Novikov  1 ,  Vladimir T Valuev-Elliston ,  Denis A Babkov ,  Maria P Paramonova ,  Alexander V Ivanov ,  Sergey A Gavryushov ,  Anastasia L Khandazhinskaya ,  Sergey N Kochetkov ,  Christophe Pannecouque ,  Graciela Andrei ,  Robert Snoeck ,  Jan Balzarini ,  Katherine L Seley-Radtke
Affiliations
  • 1. Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
PMID: 23357038 DOI: 10.1016/j.bmc.2012.12.027
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.