HIV protease inhibitors: synthesis and activity of N-aryl-N'-hydroxyalkyl hydrazide pseudopeptides

Eur J Med Chem. 2005 May;40(5):445-51. doi: 10.1016/j.ejmech.2004.11.016. Epub 2005 Feb 24.

Abstract

We describe the synthesis and activities of a series of pseudopeptides containing an N-aryl-N'-hydroxyalkyl hydrazide core structure to inhibit human immunodeficiency virus protease and viral replication. Of the series, compound Hmb-Leu-N(Bzl)-N(CH2-CH-OH)-rPro-Boc (24) displayed the greatest inhibitory potency (IC50 < 1 microM) and exhibited enzymatic resistance and stability in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / physiology
  • Humans
  • Hydrazines / chemical synthesis*
  • Hydrazines / chemistry
  • Hydrazines / pharmacology
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • HIV Protease Inhibitors
  • Hydrazines
  • Peptides