3,3a-Dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones are potent non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem Lett. 2001 Jan 22;11(2):211-4. doi: 10.1016/s0960-894x(00)00624-7.

Abstract

A series of unique 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones and a 2a,5-dihydro-2H-thieno[4,3,2-de]quinazo-line-4(3H)-thione were found to be HIV-1 non-nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed an IC90 = 4.6 nM against wild-type virus in a whole cell antiviral assay and had an IC90 = 76 and 897 nM against the clinically significant K103N and K103N/L100I mutant viruses, respectively.

MeSH terms

  • Binding Sites
  • Combinatorial Chemistry Techniques
  • Drug Resistance
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / genetics
  • Heterocyclic Compounds, 2-Ring / chemical synthesis
  • Heterocyclic Compounds, 2-Ring / pharmacology
  • Heterocyclic Compounds, 3-Ring / chemical synthesis
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Point Mutation
  • Pyrans / chemical synthesis
  • Pyrans / pharmacology*
  • Quinazolines / chemical synthesis
  • Quinazolines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds, 2-Ring
  • Heterocyclic Compounds, 3-Ring
  • Pyrans
  • Quinazolines
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase