Non-nucleoside HIV-1 reverse transcriptase inhibitors, Part 7. Synthesis, antiviral activity, and 3D-QSAR investigations of novel 6-(1-naphthoyl) HEPT analogues

Chem Pharm Bull (Tokyo). 2006 Sep;54(9):1248-53. doi: 10.1248/cpb.54.1248.


A series of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) analogues bearing a 6-(1-naphthoyl) group of non-nucleoside human immunodeficiency virus (HIV) reverse transcriptase inhibitors were synthesized and evaluated for their activity against HIV-1 and HIV-2. It was found that most of these compounds showed good activity against HIV-1. Among them, compound 5-isopropyl-6-(1-naphthoyl)-1-[(2E)-3-phenylallyl]-2,4-pyrimidinedione (23) displayed the greatest inhibitory potency (IC(50)=0.14 muM), which is about 35-fold more active than HEPT and DDI. To rationalize the relationships between structure and activity of these novel compounds, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also generated. The results provided a tool for guiding the further design of more potent antiviral agents and for predicting the affinity of related compounds.

MeSH terms

  • Anti-HIV Agents* / chemical synthesis
  • Anti-HIV Agents* / chemistry
  • Anti-HIV Agents* / pharmacology
  • Binding Sites
  • Cell Line
  • Cell Proliferation / drug effects
  • Chemical Phenomena
  • Chemistry, Physical
  • Drug Design
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / chemistry
  • Humans
  • Hydrogen Bonding
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Quantitative Structure-Activity Relationship*
  • Reverse Transcriptase Inhibitors* / chemical synthesis
  • Reverse Transcriptase Inhibitors* / chemistry
  • Reverse Transcriptase Inhibitors* / pharmacology
  • Stereoisomerism
  • Thymine / analogs & derivatives*
  • Thymine / chemical synthesis
  • Thymine / chemistry
  • Thymine / pharmacology


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • 1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine
  • HIV Reverse Transcriptase
  • Thymine