P1' oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4651-4. doi: 10.1016/j.bmcl.2004.06.092.

Abstract

HIV-1 protease inhibitors (PI's) bearing 1,3,4-oxadiazoles at the P1' position were prepared by a novel method involving the diastereoselective installation of a carboxylic acid and conversion to the P1' heterocycle. The compounds are picomolar inhibitors of native HIV-1 protease, with most of the compounds maintaining excellent antiviral activity against a panel of PI-resistant strains.

Publication types

  • Comparative Study

MeSH terms

  • Cell Line, Tumor
  • Drug Resistance, Multiple, Viral
  • HIV Protease Inhibitors / chemical synthesis
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / isolation & purification
  • Humans
  • Indinavir / analogs & derivatives
  • Indinavir / chemical synthesis
  • Indinavir / chemistry
  • Indinavir / pharmacology
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Pyridines / chemistry
  • Stereoisomerism

Substances

  • HIV Protease Inhibitors
  • Oxadiazoles
  • Pyridines
  • Indinavir