Synthesis of alkenyldiarylmethanes (ADAMs) containing benzo[d]isoxazole and oxazolidin-2-one rings, a new series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors

Eur J Med Chem. 2009 Mar;44(3):1210-4. doi: 10.1016/j.ejmech.2008.09.013. Epub 2008 Sep 19.


As a continuation of efforts to replace the metabolically labile methyl esters of lead alkenyldiarylmethanes (ADAMs) with stable bioisosteres, compounds bearing benzo[d]isoxazole and oxazolidine-2-one rings were designed and evaluated as a new series of potent HIV-1 non-nucleoside reverse transcriptase inhibitors with anti-HIV activity. All of the resulting ADAMs were found to inhibit HIV-1 RT with poly(rC) x oligo(dG) as the template primer. The most promising compound in this series was ADAM 3, with EC(50) values of 40 nM (vs HIV-1(RF)) and 20 nM (vs HIV-1(IIIB)). Compound 3 also inhibited HIV-1 reverse transcriptase with an IC(50) of 0.91 microM. ADAM 4 has an antiviral EC(50) of 0.6 microM in CEM-SS cells and a plasma half-life of 51.4 min.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • HIV-1 / drug effects
  • Humans
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology
  • Magnetic Resonance Spectroscopy
  • Oxazolidinones / chemical synthesis*
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectroscopy, Fourier Transform Infrared


  • Isoxazoles
  • Oxazolidinones
  • Reverse Transcriptase Inhibitors