Synthesis and biological evaluation of novel 5-alkyl-2-arylthio-6-((3,4-dihydroquinolin-1(2H)-yl)methyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

Bioorg Med Chem. 2011 Jul 15;19(14):4366-76. doi: 10.1016/j.bmc.2011.05.024. Epub 2011 May 23.


A series of novel S-DABO analogues of 5-alkyl-2-arylthio-6-((3,4-dihydroquinolin-1(2H)-yl)methyl)pyrimidin-4(3H)-ones were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were compounds 6c1,6c6, and 6b1 (EC(50)=0.24 ± 0.05, 0.38 ± 0.13, 0.39 ± 0.05 μM, respectively), which possess improved or similar HIV-1 inhibitory activity compared with nevirapine (NVP) (EC(50)=0.21 μM) and delavirdine (DLV) (EC(50)=0.32 μM). None of these compounds were active against HIV-2 replication. Furthermore, enzyme inhibitory assays were performed with selected derivatives against HIV-1 wtRT, confirming that the main target of these compounds is the HIV-1 RT and these new S-DABOs are acting as NNRTIs. The preliminary structure-activity relationship (SAR) of these new congeners is discussed briefly and rationalized by docking studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-2 / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase