Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains

Bioorg Med Chem Lett. 2005 Dec 15;15(24):5499-503. doi: 10.1016/j.bmcl.2005.08.093. Epub 2005 Oct 3.

Abstract

As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P(1)' ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.

MeSH terms

  • Aza Compounds / chemical synthesis
  • Aza Compounds / pharmacology
  • Drug Design
  • Drug Resistance, Multiple
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • Ligands
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Ritonavir / chemical synthesis
  • Ritonavir / therapeutic use
  • Structure-Activity Relationship
  • Urea / analogs & derivatives
  • Urea / chemical synthesis
  • Urea / pharmacology

Substances

  • Aza Compounds
  • HIV Protease Inhibitors
  • Ligands
  • Urea
  • Ritonavir