Synthesis and antiviral activity of 1,3-disubstituted uracils against HIV-1 and HCMV

Antivir Chem Chemother. 2003 Sep;14(5):271-9. doi: 10.1177/095632020301400506.


The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) is an efficient strategy for finding new therapeutic agents against human immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives have been prepared in order to explore new NNRTIs. However, there are few approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives. Therefore, we tried to prepare several 1,3-disubstituted uracils, which were easily obtainable from uracil by preparation under alkali and Mitsunobu conditions, and examined their antiviral activity against HIV-1 and human cytomegalovirus (HCMV). We found that 1-benzyl-3-(3,5-dimethylbenzyl)uracil and 1-cyanomethyl-3-(3,5-dimethylbenzyl)-4-thiouracil showed powerful inhibition against HCMV and HIV-1, respectively.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cytomegalovirus / drug effects*
  • HIV-1 / drug effects*
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Thiouracil / analogs & derivatives
  • Uracil / analogs & derivatives*


  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
  • Uracil
  • Thiouracil