Structure-activity relationship studies on new DABOS: effect of substitutions at pyrimidine C-5 and C-6 positions on anti-HIV-1 activity

Antivir Chem Chemother. 2001 Jan;12(1):37-50. doi: 10.1177/095632020101200102.

Abstract

Several 5-alkyl, 5-alkenyl, 5-iso-alkyl, 5-halo, 5-aminomethyl and 5-carboxy derivatives of S-DABOs (dihydro-alkyl (or cyclo-alkyl)thio-benzyloxopyrimidines), DATNOs (dihydro-alkylthionaphthylmethyl-oxopyrimidines) and F2-S-DABOs (dihydro-alkyl (or cyclo-alkyl)thio-2,6-difluorobenzyl-oxopyrimidines) have been prepared and tested as anti-HIV-1 agents. S-DABO derivatives bearing at C-6 position monosubstituted phenylmethyl or heteroarylmethyl units have also been synthesized. 2-Alkylthio-3,4-dihydropyrimidin-4(3H)-one derivatives of F2-S-DABO series bearing small alkyl groups at C-5 proved to be potent inhibitors of HIV-1 replication in vitro with selectivity indexes ranging from 250 to >2,500.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / toxicity
  • Cell Line
  • Chemical Phenomena
  • Chemistry, Physical
  • Drug Design
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • HIV-2 / drug effects*
  • HIV-2 / physiology
  • Humans
  • Molecular Structure
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology
  • Pyrimidinones / toxicity
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / toxicity
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors