Synthesis, antiviral activity and pharmacokinetics of P1/P1' substituted 3-aminoindazole cyclic urea HIV protease inhibitors

Bioorg Med Chem Lett. 2003 Feb 24;13(4):605-8. doi: 10.1016/s0960-894x(02)01064-8.

Abstract

A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and pharmacokinetics are described.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Dogs
  • Drug Resistance
  • HIV / drug effects
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / pharmacology*
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis
  • Heterocyclic Compounds, 4 or More Rings / pharmacokinetics
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Hydrophobic and Hydrophilic Interactions
  • Protein Binding
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*

Substances

  • DMP 850
  • DMP 851
  • HIV Protease Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • Urea