Inhibition of HIV-1 capsid assembly: optimization of the antiviral potency by site selective modifications at N1, C2 and C16 of a 5-(5-furan-2-yl-pyrazol-1-yl)-1H-benzimidazole scaffold

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7512-7. doi: 10.1016/j.bmcl.2012.10.034. Epub 2012 Oct 16.

Abstract

A uHTS campaign led to the discovery of a 5-(5-furan-2-ylpyrazol-1-yl)-1H-benzimidazole series that inhibits assembly of HIV-1 capsid. Synthetic manipulations at N1, C2 and C16 positions improved the antiviral potency by a . The X-ray structure of 33 complexed with the capsid N-terminal domain allowed identification of major interactions between the inhibitor and the protein.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Capsid Proteins / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • HIV-1 / drug effects*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • 5-(5-furan-2-yl-pyrazol-1-yl)-1H-benzimidazole
  • Antiviral Agents
  • Benzimidazoles
  • Capsid Proteins