A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1266-9. doi: 10.1016/j.bmcl.2006.12.009. Epub 2006 Dec 15.

Abstract

We have synthesized novel phosphonic acid analogues of beta-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest.

Publication types

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

MeSH terms

  • Acetoacetates / pharmacology
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • HIV Infections / drug therapy
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Ketones
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / pharmacology
  • Structure-Activity Relationship

Substances

  • Acetoacetates
  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Ketones
  • L 708906
  • Organophosphonates