1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents

Bioorg Med Chem. 2011 Oct 1;19(19):5794-802. doi: 10.1016/j.bmc.2011.08.025. Epub 2011 Aug 17.


Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Benzophenones / chemistry
  • Cell Line
  • Drug Resistance, Viral / drug effects
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Uracil / analogs & derivatives*
  • Uracil / chemical synthesis
  • Uracil / pharmacology


  • Benzophenones
  • Reverse Transcriptase Inhibitors
  • Uracil
  • benzophenone
  • HIV Reverse Transcriptase