Design and optimisation of potent gp120-CD4 inhibitors

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5250-5. doi: 10.1016/j.bmcl.2009.06.102. Epub 2009 Jul 4.

Abstract

The synthesis and structure-activity relationship of a series of novel gp120-CD4 inhibitors are described. Pharmacokinetic studies and antiviral spectrum assessment of lead compounds led to the identification of compound 36, a potent gp120-CD4 inhibitor which exhibited antiviral potency across a spectrum of 25 clade B isolates.

MeSH terms

  • Animals
  • CD4 Antigens / metabolism*
  • Cells, Cultured
  • 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
  • Half-Life
  • Humans
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry*
  • Isoquinolines / pharmacokinetics
  • Nicotinic Acids / chemical synthesis
  • Nicotinic Acids / chemistry*
  • Nicotinic Acids / pharmacokinetics
  • Rats
  • Structure-Activity Relationship

Substances

  • CD4 Antigens
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors
  • Isoquinolines
  • Nicotinic Acids