Azido-containing aryl beta-diketo acid HIV-1 integrase inhibitors

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1215-9. doi: 10.1016/s0960-894x(03)00059-3.

Abstract

Aryl beta-diketo acids (ADK) comprise a general class of potent HIV-1 integrase (IN) inhibitors, which can exhibit selective inhibition of strand transfer reactions in extracellular recombinant IN assays and provide potent antiviral effects in HIV-infected cells. Recent studies have shown that polycyclic aryl or aryl rings bearing aryl-containing substituents are components of potent members of this class. Reported herein is the first use of azido functionality as an aryl replacement in beta-diketo acid IN inhibitors. The ability of azido-containing inhibitors to exhibit potent inhibition of IN and antiviral protection in HIV-infected cells, renders the azide group of potential value in the further development of ADK-based IN inhibitors.

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology
  • Azides / chemical synthesis
  • Azides / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • HIV / drug effects
  • HIV Integrase / drug effects*
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / pharmacology
  • Humans
  • Indicators and Reagents
  • Keto Acids / chemical synthesis
  • Keto Acids / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Conformation
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Azides
  • HIV Integrase Inhibitors
  • Indicators and Reagents
  • Keto Acids
  • Recombinant Proteins
  • HIV Integrase