Furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acid derivatives: novel classes of heparanase inhibitor

Bioorg Med Chem Lett. 2005 May 2;15(9):2295-9. doi: 10.1016/j.bmcl.2005.03.014.

Abstract

Using a furanylthiazole acetic acid as a starting point, a novel series of benzoxazol-5-yl acetic acid derivatives have been identified as heparanase inhibitors. Several compounds possess an IC50 of approximately 200 nM against heparanase, for example, trans 2-[4-[3-(3,4-dichlorophenylamino)-3-oxo-1-propenyl]-2-fluorophenyl]benzoxazol-5-yl acetic acid (16e). Several of the compounds show anti-angiogenic properties. Improvement to the DMPK profile of compounds has provided compounds of potential use in in vivo models.

MeSH terms

  • Acetates / chemical synthesis
  • Acetates / chemistry
  • Acetates / pharmacology*
  • Animals
  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / blood
  • Kinetics
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Acetates
  • Benzoxazoles
  • Enzyme Inhibitors
  • Thiazoles
  • heparanase
  • Glucuronidase