Structure-based design, synthesis and biological evaluation of new N-carboxyphenylpyrrole derivatives as HIV fusion inhibitors targeting gp41

Bioorg Med Chem Lett. 2010 Jan 1;20(1):189-92. doi: 10.1016/j.bmcl.2009.10.139. Epub 2009 Nov 5.

Abstract

A new series of N-carboxyphenylpyrrole ligands were designed using GeometryFit based on an X-ray crystal structure of gp41. The synthesized ligands showed significant inhibitory activities against HIV gp41 6-helix bundle formation, HIV-1 mediated cell-cell fusion and HIV-1 replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / metabolism
  • HIV Fusion Inhibitors / chemical synthesis*
  • HIV Fusion Inhibitors / chemistry
  • HIV Fusion Inhibitors / pharmacology
  • Humans
  • Protein Binding
  • Protein Structure, Secondary
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology
  • Thermodynamics

Substances

  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Pyrroles