Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1241-6. doi: 10.1016/j.bmcl.2009.11.123. Epub 2009 Dec 5.

Abstract

A series of stereochemically defined cyclic ethers as P2-ligands were incorporated in an allophenylnorstatine-based isostere to provide a new series of HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cricetinae
  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical / methods
  • Furans / chemistry*
  • Furans / metabolism
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / metabolism*
  • Humans
  • Ligands
  • Phenylbutyrates / chemical synthesis*
  • Phenylbutyrates / metabolism*
  • Protein Binding / physiology
  • Stereoisomerism

Substances

  • Furans
  • HIV Protease Inhibitors
  • Ligands
  • Phenylbutyrates
  • tetrahydrofuran
  • 3-amino-2-hydroxy-4-phenylbutanoic acid
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1