Discovery of a small molecule inhibitor through interference with the gp120-CD4 interaction

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5246-9. doi: 10.1016/j.bmcl.2009.06.080. Epub 2009 Jun 25.

Abstract

A series of piperazine derivatives were designed and synthesised as gp120-CD4 inhibitors. SAR studies led to the discovery of potent inhibitors in a cell based anti viral assay represented by compounds 9 and 28. The rat pharmacokinetic and antiviral profiles of selected compounds are also presented.

MeSH terms

  • Animals
  • Biological Availability
  • CD4 Antigens / metabolism*
  • Cell Line, Tumor
  • Drug Design
  • HIV Envelope Protein gp120 / antagonists & inhibitors*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Fusion Inhibitors / chemical synthesis
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / pharmacokinetics
  • HIV-1 / drug effects
  • Humans
  • Microsomes, Liver / metabolism
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacokinetics
  • Rats
  • Structure-Activity Relationship

Substances

  • CD4 Antigens
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors
  • Piperazines