Aqueous stability of SB 210661: kinetics and primary degradation mechanisms of an N-hydroxyurea-containing 5-lipoxygenase inhibitor

J Pharm Pharmacol. 1998 Feb;50(2):127-32. doi: 10.1111/j.2042-7158.1998.tb06166.x.

Abstract

SB 210661, (S)-N-hydroxy-N-[2,3-dihydro-6-(2,6-difluorophenylmethoxy)-3-benzo furanyl]urea, is a potent and selective inhibitor of 5-lipoxygenase. Its aqueous stability was primarily evaluated to support development of analytical methods and formulations. The results also add to the growing database on the stability of N-hydroxyurea compounds. Comparison of the stability of SB 210661 with that of two other N-hydroxyurea-containing compounds, zileuton and Abbott-79175, supported a common primary degradative pathway at pH > 5 and different degradative pathways at pH < 5. The pathway at pH > 5 is consistent with the hydrolysis of the N-hydroxyurea group, whereas for SB 210661, the pathway at pH < 5 is consistent with specific acid-catalysed nucleophilic displacement of the N-hydroxyurea group by water.

MeSH terms

  • Benzofurans / chemistry*
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Hydroxyurea / analogs & derivatives
  • Hydroxyurea / chemistry
  • Kinetics
  • Lipoxygenase Inhibitors / chemistry*
  • Urea / analogs & derivatives*
  • Urea / chemistry
  • Water

Substances

  • Benzofurans
  • Lipoxygenase Inhibitors
  • SB 210661
  • Water
  • A 78773
  • Urea
  • zileuton
  • Hydroxyurea