Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4213-7. doi: 10.1016/j.bmcl.2007.05.039. Epub 2007 May 17.

Abstract

We designed several HIV protease inhibitors with various d-cysteine derivatives as P(2)/P(3) moieties based on the structure of clinical drug candidate, KNI-764. Herein, we report their synthesis, HIV protease inhibitory activity, HIV IIIB cell inhibitory activity, cellular toxicity, and inhibitory activity against drug-resistant HIV strains. KNI-1931 showed distinct selectivity against HIV proteases and high potency against drug-resistant strains, surpassing those of Ritonavir and Nelfinavir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Cell Line
  • Cysteine / chemistry*
  • HIV / drug effects
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Phenylbutyrates / chemical synthesis*
  • Phenylbutyrates / chemistry
  • Phenylbutyrates / pharmacology*
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Amides
  • HIV Protease Inhibitors
  • KNI 764
  • Phenylbutyrates
  • Thiazoles
  • 3-amino-2-hydroxy-4-phenylbutanoic acid
  • Cysteine