Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1500-3. doi: 10.1016/j.bmcl.2010.01.111. Epub 2010 Jan 25.

Abstract

A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell-cell fusion assay. The observed inhibition constant of compound 7 was 2.1microM, and the IC(50) for cell-cell fusion inhibition was 1.1microM. Assay data indicated that 7 is a promising lead compound for optimization into an effective low molecular weight fusion inhibitor.

Publication types

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

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Benzoates / chemical synthesis*
  • Benzoates / chemistry
  • Benzoates / pharmacology
  • Binding Sites
  • Cell Line
  • Computer Simulation
  • Drug Design
  • HIV Envelope Protein gp41 / antagonists & inhibitors*
  • HIV Envelope Protein gp41 / metabolism
  • HIV Fusion Inhibitors / chemical synthesis*
  • HIV Fusion Inhibitors / chemistry
  • HIV Fusion Inhibitors / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Thermodynamics

Substances

  • Anti-HIV Agents
  • Benzoates
  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Indoles