Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors

J Med Chem. 2005 Nov 3;48(22):7084-8. doi: 10.1021/jm050549e.

Abstract

Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Binding Sites
  • Cell Line
  • Cytopathogenic Effect, Viral
  • Drug Design
  • HIV Integrase / chemistry*
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology
  • Humans
  • Keto Acids / chemical synthesis*
  • Keto Acids / chemistry
  • Keto Acids / pharmacology
  • Lymphocytes / drug effects
  • Lymphocytes / virology
  • Models, Molecular
  • Quantitative Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Keto Acids
  • HIV Integrase