Potent cyclic urea HIV protease inhibitors with 3-aminoindazole P2/P2' groups

Bioorg Med Chem Lett. 1998 Apr 7;8(7):715-20. doi: 10.1016/s0960-894x(98)00118-8.

Abstract

Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a Ki < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • HIV Protease / chemistry
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemical synthesis
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology
  • Indazoles / chemistry*
  • Indazoles / pharmacology
  • Indicators and Reagents
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • HIV Protease Inhibitors
  • Indazoles
  • Indicators and Reagents
  • Urea
  • HIV Protease